Jane Kramer. Photo: Dina Litovsky

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In 2017, 23andMe began offering tests for the genetic risk of developing certain health conditions like celiac disease, Parkinsons, and late-onset Alzheimers. The Alzheimers test will tell you if you have the gene variant APOE4, which means you have an increased likelihood of developing the disease. One in four people carry a single copy of the gene, but 2 to 3 percent of the population have two copies one from each parent and have a much higher probability. As with all of 23andMes upcharged Health Predisposition Reports, the sell on it was self-empowerment: Once you know, you can plan, allowing you to take charge of your well-being.

Except most experts dont recommend that you test for APOE4 status. Theres no cure for Alzheimers disease and no surefire way to prevent it. Many people who find out they have two copies of APOE4 from 23andMe are left only with profound anxiety. Not taking the test in a clinical setting means that when the results come in, there is no doctor or counselor present to help process them or explain what can even be done with the information. Instead, theres the internet: In Facebook groups and Reddit forums, APOE4/4s, as they call themselves, try to help one another through their doom spirals. They parse scientific studies on the links between exercise and cognition and theorize about the protective benefits of fish-oil supplements and cooking with saffron.

In 2022, the actor Chris Hemsworth revealed in the National Geographic docuseries Limitless that he has two copies of APOE4, prompting a wave of interest in getting tested. Peter Attia, the longevity doctor who gave Hemsworth the news in the series, devoted a chapter of his 2023 book, Outlive: The Science & Art of Longevity, to the gene variant, proposing a series of lifestyle changes to manage your genetic risk up your fish consumption, cut out alcohol, lift weights, hit the dry sauna four times a week some of which are more speculative than solidly proved. Still, his recommendations are a mainstay of online-community discussions.

In May, Nature Medicine published a study that recommended reclassifying APOE4/4 status as not just a risk factor for developing Alzheimers but a clear cause news that sent many 4/4s spinning. Some plunge themselves into research, looking for methods to stave it off. Others compartmentalize (and philosophize) while trying to be present in their lives. Here, ten 4/4s stories.

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Jane Kramer, 58, Scarsdale

My dad died of Alzheimers. He was about 73 when he became forgetful. He ended up living till just about 87, so it was many, many years of decline that I was witness to. When my older sister was 64, my niece came to me saying theres something going on. I knew what was going on. Theres something called a MoCA test; its a classic test they give people to see where they are in their cognition. And the mini mental-state exam, I think it is MMSE. Its like, Draw a clock, make it be ten minutes after 11. Draw this shape. Here are three words, remember them. Now Im going to talk to you and divert your attention for 20 minutes, then come back. What are those three words? Things like that. I was with my sister when she took this test and she failed miserably. It was probably one of the saddest moments of my life.

When this all happened, that made me go, Uh-oh, I am screwed. These are two first-degree relatives now. When I got the genetic results, I 100 percent freaked out. I became mentally fatalistic, was drinking more. I have always been quite healthy in my life, and I thought, Oh, Im ruining things.

The kind of person I am, I decided, Im gonna find every clinical trial there is. I managed to get into the Weill Cornell Alzheimers Prevention Clinic and started getting blood work and cognitive testing every six months. I signed up for some clinical trials I knew I would never participate in, just to get tests because you cant get certain tests otherwise. I got free MRIs. I got free plasma-biomarker tests. I participated in the Womens Brain Initiative with Dr. Lisa Mosconi, whos a bigwig. Theres a new drug thats in an extended phase-three trial, so Im in touch with the head of that drug company. I have no shame. There was a press release and the guys email was on it, so Im like, Hey, hows it going? Im wondering if youre doing any prevention trials.

I did all these studies for years. Then I was going to get an amyloid PET scan and I stopped. I realized I didnt want to know if I had a positive amyloid PET. I was like, Youre just trying to hurt yourself by knowing too much.

My sister is 70 now and is about to go into hospice. Its been a fairly fast decline. She doesnt know who anyone is, speaks babble, and its really bad. As I get closer to the age of my sisters diagnosis, I get more stressed out. As you get older, there is normal forgetfulness sometimes, like when you dont get enough sleep. So I ask my nieces, What were the first signs you saw in my sister? I want to know what made them think it wasnt just forgetting. Its a learning experience every day: How do I filter whats normal from what isnt normal? I did have an MRI again recently, and I could compare it to my first one, in 2019 I always ask for the disc and everything so I can compare. My brain is still the normal volume; my hippocampus is still the right size. I remember seeing my sisters MRI when she was diagnosed, and her brain was like half the size of her head. So that makes me feel better.

If I think about it too much, I get scared. When I see my sister on FaceTime, I get really, really sad. I dont have kids, but Ive already given my nieces permission not to come visit me because its too upsetting. One question I have is, Do I have enough money to not have to be thrown in a home? Im married to a nurse practitioner, and shes a planner. She wants to know how much I wanna be taken care of. Like, How much intervention do you want? Thereve been fights about it. I want to be taken care of properly; I dont want to be left in my own shit or fall down and hurt myself. But could she maybe and Im okay with this not force me to eat if I dont know what eating is? That comforts me because I know that starving to death is not painful, right? If I lose the hunger mechanism, if I dont know what food is and its sitting in front of me and I dont know what to do with it, shes not gonna put it in my mouth. I think her knowledge will create a much more humane situation at end of life for me, if thats the case. I dont know if Im brave enough to go and do an assisted-death thing. Im chicken about that stuff.

Jake Petersen. Photo: Dina Litovsky

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Jake Petersen, 33, Los Angeles

I signed up for 23andMe because I was more interested in questions like Does cilantro taste bad to me? I didnt give the genetic risk much thought. Then I read the Peter Attia book. All of a sudden, I got extremely nervous. I felt like a train had hit me.

I went into full research mode. Nights, weekends, I had a Google Chrome window with 80 tabs on it, bookmarks out the wazoo. In this time, Ive learned how to read scientific studies, and Ill use ChatGPT to digest a lot of them when I cant understand. As someone in their 30s, Im not really finding any resources available I guess its in none of these studies interest to put someone in the study in their 30s because theyre not going to find out the results for, what, 40 years?

I consider myself extremely lucky and extremely pleased that I found this out. Alzheimers is something thats starting in my brain now. The plaque these buildups are happening in my 30s, right? I want to change these odds as much as possible. Im optimistic, but I hear this clock ticking in the back of my head.

Im not overweight. I do cardio. I do HIIT, I do Barrys Bootcamp. Im not a net risk factor. But I think for me, the first step was, Okay, Jake, you need to get a doctor thats going to not laugh at you when you bring this up and say, Youre 30, dont worry about it. Youre healthy, youre fine.

So I ended up joining Forward, a membership health clinic. They talk about medicine 3.0 and use software to track your health and vitals over time. From reading Peters book, I started to understand the litany of tests I wanted to get done. An APOE4 carrier does have challenges with cholesterol and processing lipids. We have a pretty high family history of cholesterol; everyones on a statin. So I did an advanced lipid panel: It shows your ApoB, your density of particles, how much small dense LDL you have. That ones the worst its more likely to cause issues in both cardiovascular disease and with Alzheimers because essentially Alzheimers is partially a lipid-transport disease. The panel showed that my LDL is a bit high, but looking at the ApoB and the small dense LDL, Im somewhat close to off the charts. Im probably going to have to go on a statin in the next couple of months.

I started doing a lot of research into different scientific studies. I have a note on my iPhone Notes app thats superlong: I add everything Im learning so I can reference it when I talk to people or talk to doctors. For me, the knowledge is comforting. My cousin got married in May; it was a big family wedding, and I shared Outlive and the chapter on Alzheimers with my entire extended family. Ive asked my cousins, When was the last time you got your cholesterol checked? Ive become the nutty cousin.

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Anonymous, 41, New Jersey

My father is very into genealogy, so on a whim, we did 23andMe. At some point, I logged on and it said, Were now testing for the Alzheimers gene. Click this button if you want these results. And I was like, Okay, whatever. So I clicked it. I didnt think much about my results. Then a couple years go by and Chris Hemsworth started talking about this, and I was like, Oh my God.

I pretty much had a nervous break. Im a person who runs a tight ship: Im always getting a million things done, and it was alarming for my husband because hes never really seen me so emotional. I was crying a lot, and I wasnt eating. Everything I was reading about APOE4 talks about the plaques on your brain, which they say you can prevent through fasting and maintaining a certain diet and being thin. I dont know if its even healthy, but I became hyperfixated on being thin so I dont cause plaques on my brain.

Every day, I wish I could go back, that I had never found out this information. Knowing my APOE status drives my entire life. I used to be a very, very social person. I have lots of friends, I would have wine nights with them, I would go out every weekend. My kids are 12, 9, and 7, and its not like I didnt spend time with them I just had an active life outside of them, too. That has significantly declined. Now I dont like to leave my family. I dont want to be away from my kids. I dont want to miss anything with them. I only work two days a week now so I can be with them, go to all their sporting events, and drive them everywhere. Im also constantly stressed about going out and drinking because I know drinking alcohol can cause plaques in your brain, too. I do feel like knowing this status has changed who I used to be. So much of my identity now is how my kids do, and I dont know if thats healthy, either. But I get so upset because I feel like Im going to miss out on all their lives.

A couple months ago, I tried to get long-term-care coverage because of all this. We found a really solid plan I was giddy with excitement because it would provide exactly what I was looking for. It was hard to even explain it to our financial planner because its a weird request for somebody to make at 40. This is a policy people take out in their 60s. It was going to cost us an insane amount in premiums: $100,000 over the course of ten years. No normal person would pay it, but my husband was willing to because we knew itd provide me complete peace of mind. Like if something does happen to me, at least there is a plan in place for me and my family. I didnt disclose to the insurance company about the 23andMe stuff or the APOE genes because then I would never have gotten the policy. But I ended up getting denied for the plan anyway because Im too thin.

The foundational question about this type of genetic testing is whether it is actually beneficial to people. I was frustrated with 23andMe because theyre giving you such heavy information with no context, no background. Its like somebody telling you youre gonna get cancer and then thats the end of it. Let me tell you, with this information, there are no resources for me. If it were a breast-cancer gene I got, I would just go get surgery and take my breasts off. There would be a plan. With the APOE4, I could barely get an appointment with a neurologist. They did not want to see me unless I was having cognitive issues, but Im not because Im only 41 years old. I reached out to 23andMe because I was having so much anxiety, and I also talked to an independent genetic counselor. They said to me that their results are not 100 percent accurate. Their results could be wrong. I could be making myself sick over this, and this might never even happen. If you do retest, then that becomes a part of your medical history. Health insurance cant deny you because of these things, but life-insurance and long-term-care plans absolutely can. Once its in your chart, itll haunt you forever.

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Charlotte, 34, New Haven, Connecticut

I have an autism diagnosis: ASD1, which has the lowest support needs. I was in school and just trying to manage my life and my executive dysfunction. That was my overall issue: not feeling capable of brushing my hair and taking a shower and going to school and going to work in the same day. So I was looking into genetic testing to see if, aside from just being highly medicated, there was some way to help long term. But the only interesting thing on my genetic testing was the APOE4 genes.

I felt like there was some mystery to be unlocked like I could figure out if I just Googled enough. I started getting certain supplements and going to the sauna all the time because they said the heat-shock proteins are supposed to clear out the plaques in your brain. I did some cryotherapy. I started growing lions mane, which is supposed to have neuroregenerative effects; I sourced a log to put in my backyard, which I inoculated with spores. Then my friend whos a researcher made a comment. He said something like The reason self-help books and these podcasts are so popular, especially in America, is because they give us the illusion of control and productivity, even if there isnt really. And my explosive problem-solving process was just more to feel like I have control of my destiny than that I actually gained control of anything. I grew up on a farm and we had working dogs, and if theyre not doing something, theyre tearing up the couch. It felt like the same energy: all these people having to put their energy toward something even if its not the Solution.

I will say that knowing my APOE4 status changed the trajectory of my life planning. Before, I didnt know if I wanted kids. Then I think I just softened toward the idea of having a family because if my life is gonna be short anyway, I just wanted to give part of myself while I still have it. I was going to school and was pretty focused on doing something in the medical field; I was taking some premed and nursing classes. Now the timeline was shortened a little bit. If it looks like I can only successfully work until Im 70, then will I have enough time in my 30s to finish a minimum eight-year education, then pay off student debt? How much time do I even have to accomplish this? Im taking a break from school now, but if I were to go back, Ill probably focus on something that utilizes mind power, so I can stay sharp, but that wont require taking on as much debt because I dont know how much time I have to pay it off.

You know whats so weird? After getting my results, I actually started being nicer. I was always very shy and really reserved, and I would be grumpy toward anybody that was, like, trying to be nice to me, maybe because I didnt feel like I had the bandwidth for it. But Ive almost started taking myself less seriously, maybe almost in a self-preservation sense. Because if Im gonna be really grumpy and unpleasant and crazy and have no faculties in, like, 30 years, Im gonna need a community. This is something I should start preparing myself for now.

I just had a baby. Im 34, my husband is 38. If this affects me around 75, then my kids would only know me until theyre my age and my husbands age. I just want to make sure Im as good to the people around me for as long as I can be, until I cant be.

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Rebecca Haddad, 34, Pittsburgh

When I was in school to be a physicians assistant, I was in a working group and our discussion topic was the ethics of take-home DNA tests. Youre opening Pandoras box and giving these tests to people who dont have a good grasp on where to fit these answers into the puzzle of their whole life. You could get a negative DNA-test result and be like, Oh, like, Im in the clear, not go to your preventive appointments, and have this false sense of security. But at the same time, you dont want to live your life just so terrified of something thats so out of your control. In my group that day, Alzheimers specifically came up. Everybody was saying, Oh my God, I would never want to know. And I was just sitting there like, Yeah, man, thatd be really terrible, knowing full well that I already had this information.

When I first got my results, I made a choice. I dont want to live my life so tied up in this genetic finding. I could live my whole life taking choline and all these supplements and I could still get it. Or I could do none of those things and never get the disease. Or I could get hit by a bus tomorrow on my way to work.

About six months ago, I was dating a doctor at my work. I told him about my APOE4 status because I thought, of all people, he would understand what this test result meant. I thought he would be like, Okay, it wasnt a big deal. But he had this very overblown reaction. He was like, Thats an early Alzheimers indicator. You need to go to a geneticist and get this testing done. It was devastating not because I wanted that relationship to continue, but his reaction almost validated these huge scary feelings Id had about it when I first got my results.

Donna Dorans. Photo: Dina Litovsky

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Donna Dorans, 70, Agawam, Massachusetts

When I found out, I was sort of numb. Then I started researching. Googling. Im an occupational therapist, so I understand a lot of medicine and I was looking at the real details of what happens to the brain. I became very anxious. My family thought I was going crazy. With the APOE4, what happens is that eventually you have problems with glucose in the brain. So I started changing how I ate. Ketosis is recommended by a lot of people. So I started cutting out a lot of carbs.

What was going through my head was, If Im not going to prevent it, maybe I can stall it as much as I can. I have to follow this protocol. It backfired. Some of the diets are so restrictive that you start eliminating things you probably shouldnt. I had started losing weight because I was trying to cut back on carbs, but Im a small person to begin with. Thats not healthy for muscles, and at my age, you start losing muscle mass. I used to drink a lot of milk, but I was also trying to cut back on dairy and trying to get calcium through other foods, which I later realized wasnt good for my bones. Small people are more at risk for osteoporosis, which I did develop. I was never a big red-meat eater but would eat some here and there; then I stopped and later learned I wasnt getting my iron. I started eating a lot more vegetables, but if you eat a lot of certain vegetables that are cruciferous or raw, it can interfere with your thyroid. I started having thyroid trouble. I wasnt getting enough iodine because of the way I was eating.

Ive learned the hard way that whats supposedly healthy isnt always as healthy as you think. I tried to add some stuff back into my diet. Still, my biggest fear is that its going to start soon. Theres times when I think, Oh, is this it? But so far, it hasnt yet that I know of.

Brett Memsic. Photo: Dina Litovsky

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Brett Memsic, 39, Los Angeles

The biggest way this has affected my day-to-day life is my paranoia about forgetting things. From the time I was in high school, I felt like I remembered everything almost photographically. But now my friends will remember stories from a couple of years ago or quotes from movies that I dont. When things like that happen, I spiral a bit more. If I cant remember something, I dwell on it for like 12 hours until I do. In conversations with my fiance, Ill get stuck on trying to remember everything and bring her into it; we cant advance the conversation and talk about something else until I remember it. Its a constant thing in the back of my head whenever I forget something or whenever I dont remember something immediately: Is this happening now or sooner than normal? Is it a linear thing where Im actually like 15 percent impacted by this and just dont know it yet?

In general, Im pretty nonreactive to bad things happening. I maintain a similar baseline. But Monday, May 6, 2024, was a turning point for me. In my last couple years after getting the test, it was like, Well, this thing exists, but there was enough deniability or enough of a likelihood that I wasnt gonna get it. What was so scary about this study the New York Times wrote about that Monday was that theres potentially a causal link between the APOE4 allele and Alzheimers, and it may be more of a guarantee. It made it a lot more real. My fiance and I had a conversation where I broke down a bit because its like, This affects you a lot, too. Were getting married in October. Later, I mentioned my APOE4 status to one friend and he joked that my fiance still has a couple months to upgrade to a better model.

Patricia Avvocato. Photo: Dina Litovsky

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Patricia Avvocato, 61, Rye Brook

When II read the genetic test, I was not surprised. Most of the women in my family have had a history of Alzheimers before dying. It was never diagnosed officially because they never went to doctors.

At first, I brushed it off. I said, Well, Im doing everything that I know you have to do for brain health already. I manage my sleep, my diet, and I always exercise. Ive never had junk food in my life. What else is there to do? Why torture myself?

I was in my 50s, and around that time I was more interested in making sure I did not go into menopause. It is very funny how I had never put the two together. I just wanted to have vigor and vitality. I found a rheumatologist, who put me on bioidentical hormone replacement. When I told him my APOE4 results, he said, Well, you need to go on rapamycin. Its an immunosuppressant that, at normal dosage, is used to prevent rejection of organ transplants and is used off-label for many things, including neurodegenerative diseases.

He put me in contact with this man Alan Green, in Little Neck, Long Island, whos in his 80s. And he agreed that I should go on rapamycin. So Ive been taking that for about five years. And Im in all this Wild West type of care with certain doctors who are into regenerative medicine, both here in the United States and in Colombia, where I go to visit my mom about three times a year. They dont have so many restrictions there, so Ive been able to tap into unapproved treatments.

I have a daughter whos 31 years old. I am a great believer that, if I do go on a path where there is no way to end my life with my brain intact and being able to live an independent life, she can terminate my life. Ive seen the deterioration. My mothers mother lived with her until she died, and she could barely go from one place to another in the same apartment. It was just very, very sad. Its been shown that caretakers actually start aging faster than the people with neurodegenerative diseases just from caring for them. My daughter will have a power of attorney to take me to Dignitas in Switzerland and terminate my life.

These days, I dont rush anymore. I used to be always anxious that I needed to be at a certain place at a certain time, and Id do too many things. I was working too many hours. I would exercise only on the weekend. Instead of working five days a week, Im working three days a week now because then I wanted to dedicate more time for exercise, for relaxing, for meditation. If something doesnt get done today, it doesnt get done.

Miguel Delgado. Photo: Dina Litovsky

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Miguel Delgado, 30, Los Angeles

After I found out I carried two copies of the gene, I started preaching about it to my family. I told my mother and brother, Hey, itd be nice to know if you are at risk of any diseases. It turns out were all three double-E4 carriers. But I dont think my family realizes what it means.

My mothers a very religious person. I dont know if she believes in genetic predisposition. Im sure she does to some degree, but I feel shes much more of a Maybe we can pray and make sure we dont carry them kind of thing. Its just that talking about death is taboo in a way; it seems like youre speaking it into existence.

She had a mini-stroke last year. We never got a diagnosis, but I think thats what it was. So it gets me a little worried. She doesnt eat well. Money makes a difference, right? Since she works a manual-labor job shes a quality-control inspector at a pork factory she comes home and just wants something easy. Fast food or whatever, its easy to grab. Shes very much a daily bread eater, like your classic Mexican bread, very sugary, heavy on carbs. She drinks a lot of Coke. So Ive been trying to I wouldnt say scold her about it, or maybe I do. I try to explain the severity of it and how she needs to take better care of her body.

My moms big thing is being self-reliant. So I try to convince her by saying that if she were to get something like this, that would take away from my brother and me because wed have to care for her. Im pretty hopeful. Luckily, she is fortunate enough that she could afford the salmon. She never ate salmon before. I got her eating salmon at least once a week now. So its an improvement. I even bought her Peter Attias book in Spanish, and I think she got through two chapters of it. She said she wasnt training to be a doctor or something.

My dad hasnt given me a definite answer on why he doesnt want to take the test. For a while, at least for a year, I was bringing it up every once in a while. But at the end of the day, even if I do find out if he has it, it doesnt change my genetic makeup, unfortunately.

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Jane Bailey, 74, Litchfield, Connecticut

My whole life, Ive known about dementia. When I was very young, I heard stories from my mother about my grandmother. I never met my grandmother; she died of dementia when I was only 3 years old. My mother said she probably had Alzheimers but they didnt know a lot back then about Alzheimers. She ended up in an institution. Then when I was in my 30s, my mothers sister was starting to suffer from Alzheimers. And then in my 40s, my mother-in-law developed Alzheimers.

Shes not related to me, but it was through the experience of seeing her degradation that I realized how awful a disease this is. She had always been a very organized and very elegant person, and she had set aside boxes where she had labeled what we were going to get when she died, like, Jane and Steve get the crystal and so-and-so. When the Alzheimers developed, we knew she was going to have to go into a home, and we got those boxes of things that were labeled for us. We got the crystal and put it on our credenza. One day, she came to visit us when she was going really downhill, and she said, You stole my crystal.

No, Mom, we didnt steal your crystal, we said. Thats what you gave to us.

No, I wouldnt have given away my crystal.

We would have to seat her so that her back was to the credenza so she wouldnt see the crystal and get triggered. It was the change in personality that, above all else, was very, very hard to look at: When my mother-in-law eventually died, in 1999, I couldnt even cry because she had really died a couple years before. Then my mother was diagnosed in 2008.

Two years after she died, in 2015, my daughter gave me a gift of 23andMe for Christmas. The report told me I had two copies of the gene. I was 67 at the time. By age 75, the general population has a 3 percent chance of developing Alzheimers, but I would have a 28 percent chance at my age pretty much right now. Im 74. And then for women at age 85, it jumps to a 60 percent chance versus a general population with a 14 percent chance.

I didnt feel bad about it. It was a blinking yellow caution light: Watch out, youre getting older. I wanted to be armed for a battle. I could see from watching my mother-in-law and my mother that they would lose a sense of time and not know what to do. So I said, Okay, I have to develop a really good habit for putting my keys on the hallway table. I cant put them anywhere else. I have to sleep for eight hours. I have to eat healthy. I have to do less multitasking. I always would join whatever club or organization I join and was always willing to take on a leadership position. Now, I just want to relax a little. I used to be on Facebook a lot more, and now I just feel like I dont want to waste my time on that. Id rather read or play Scrabble with my husband. Routines are more important. But I dont know how much of this is related to APOE4 and how much is just related to being 74.

If I were honest, I feel its probably inevitable that Ill develop Alzheimers. But no ones losing sleep over APOE4, least of all me. My son says, Oh, Mom, you seem fine. Im only 33, and Im already forgetting things. My husband will say, Dont worry, Ill just call the white coats and get someone in to do my laundry and cook my meals. I think, Okay, if I were to lose my memory, what is it that I want my family to do for me? I want them to understand that I need to be talked to softly. I want music thats quiet. I want somebody to read me poetry, maybe.

As she went into heavier Alzheimers, my mother got sweeter. More relaxed. She seemed able to live moment to moment and not worry about what she could remember or what she couldnt. While my mother-in-law was like, I need to remember this, and yet couldnt remember, my mother was like, Oh well, I cant remember it. She didnt seem to fight it.

Now, I keep saying two things to myself. One is to create good memories now and dont make bad memories. Make good ones because thats whats going to be there and you want them to get into long-term memory. Now, Ill consciously say to myself, This is going to be a good memory. Wow, this is a great day. I have to remember this one when Im old. But I also say to myself, Just enjoy the moment. Dont worry about whether its creating a memory or not. I guess what I dont know is, Does appreciating the moment-to-moment require memory? I will say, right now, that when you really focus on a moment, it often bridges to other moments.

For example, right this second Im looking out my dining-room window and I see a beautiful forsythia bush thats in full bloom. I cant look at it without seeing my sister and myself 50 years ago. When I was probably 8 years old, my mother took a picture of us in front of a forsythia bush at home in Staten Island. Today, Im looking at this one, and I say, God, thats a gorgeous forsythia bush. But its more than that. Its also the memory thats embedded in it.

Correction: The print edition of this story incorrectly credited the portfolios photographer. It is by Dina Litovsky.

Thank you for subscribing and supporting our journalism. If you prefer to read in print, you can also find this article in the July 15, 2024, issue of New YorkMagazine.

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Ten People on Finding Out They Have the Alzheimers Gene - New York Magazine

Recommendation and review posted by Bethany Smith

Undergoing germline testing is of particular importance for patients with prostate cancer, as one expert explained.

Germline testing is that genetic testing of the of the sequence of DNA that you inherit from your parents, so it's looking at whether you've inherited your risk for cancer, explained Dr. Kelly Stratton, associate professor of urologic oncology at the University of Oklahoma in Oklahoma City, during a conversation that was part of the CURE Speaking Out video series.

In prostate cancer, that's particularly important because it could allow us to give you treatments that can be targeted to alterations that you've inherited and may have been what predisposed you to develop prostate cancer.

Many patients with high-risk or metastatic (cancer that has spread to other parts of the body) prostate cancer are recommended to undergo germline testing, for example, Stratton said.

A lot of times urologist can be the point person for referring or conducting that testing, and that testing can also help us identify patients who may be candidates for other treatments, Stratton said. In particular, for patients who have metastatic, castration-resistant prostate cancer [cancer that grows when testosterone levels in the body are low], there are several drugs that are specifically indicated for patients who have [genetic] alterations.

However, adherence to germline testing is low. A study published in JAMA in 2023 found that, among nearly 1.4 million patients who received a diagnosis of cancer between 2013 and 2019 in California and Georgia, only 6.8% in total underwent germline testing, and only 1.1% of patients who received a diagnosis of prostate cancer were tested.

Historically, there have been a lot of a lot of barriers, both understanding the potential candidates for testing, understanding the test and how they're available, and also the potential cost to patients, Stratton said. As we continue to get more and more treatment options, I think those barriers have gone down, urologists are increasingly more comfortable referring or conducting the genetic testing, insurance companies are understanding the benefit of approving those tests and it's easier for us to communicate to patients the potential implications of the genetic test, and also the costs of the genetic tests. So, as we see more and more treatments, it becomes an easier conversation to have with patients.

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Recommendation and review posted by Bethany Smith

A woman who gifted her boyfriend an at-home DNA test for Christmas was left reeling by the results.

Diamond Jane, 25, gifted her boyfriend Garrett a 23andMe test, and when the results came back, they learned he had Neanderthal DNAand quite a lot of it.

And while Diamond Jane was "laughing" about the result, her partner finds it "empowering."

She told Newsweek: "He feels lucky to have close ties to the first humans to roam the Earth."

Neanderthals were early humans who lived around 400,000 years ago and went extinct around 40,000 years ago, and are recognized as our closest ancient human relatives.

For part of their existence, Neanderthals lived alongside early modern humans, and some bred together, with some humans inheriting Neanderthal DNA, according to the U.K.'s Natural History Museum.

And in a viral video shared to her TikTok account @diamondmaglietta on June 11, Diamond Jane first showed a photograph of the pair together before then revealing the results of the test.

It told Garrett he had "more Neanderthal DNA than 82 percent of other customers."

And, writing on the video, Diamond Jane said she found out "more than I wanted to know," but "at least we didn't find out we're related."

Having been viewed 2.5 million times and garnering 203,000 likes, the comments were filled with hundreds telling their own stories, including one who joked: "My husband found out the same thing and honestly it explains so much."

"My dad got 93 percent and swears it's a flex," another said, and one revealed their friend found out they had 89 percent: "I made fun of her relentlessly, then I did 23andMe... I have 92 percent."

"The way I would never let this go," one user wrote, with Diamond Jane replying: "I haven't."

Speaking to Newsweek, the certified nursing assistant from California said of her partner: "Growing up I've always heard of the word 'Neanderthal' as an insult but apparently, to him, it's empowering."

She explained: "I thought it would be a fun and interesting way to get to know him better and he enjoyed finding out about his family history because he's always talked about wanting to know more about it."

Genetic testing outside of a medical setting has exploded in popularity in recent years, with the likes of 23andMe, AncestryDNA, MyHeritage and more all offering ways to explore your background.

Like Garrett and some of the commenters, sometimes people can learn they have Neanderthal DNA from these tests: earlier this year, one man went viral after his test results showed he possessed 98 percent more than the average person.

At the time, Newsweek spoke to Cesar de la Fuente, a University of Pennsylvania engineering presidential assistant professor involved in research into ancient DNA.

He said: "Results like this could imply significant interbreeding between an individual's ancestors and Neanderthals, but further research is likely needed to confirm this and understand its implications accurately.

"The effects of Neanderthal DNA remains a very much active area of research."

Do you have funny and adorable videos or pictures you want to share? Send them to life@newsweek.com with some extra details, and they could appear on our website.

Newsweek is committed to challenging conventional wisdom and finding connections in the search for common ground.

Newsweek is committed to challenging conventional wisdom and finding connections in the search for common ground.

Read more from the original source:
Man Does DNA Test, Gets Result He Was Never Expecting: 'Neanderthal' - Newsweek

Recommendation and review posted by Bethany Smith

Most people are carriers for at least one genetic condition, meaning that any individual might need the help of a genetic counsellor a few times throughout their lifetime.

Last month, UK-based Sano Genetics launched Light the Way, an online support platform offering genetic testing and counselling for people suffering from motor neurone disease (MND) or with a family history of the condition.

As the demand for genetic testing and counselling booms, new approaches such as AI are being utilised to address the shortage of genetic counsellors.

Digital genetics company Igentifys digital genetic assistant (DGA) uses AI to power genetic counselling. It develops personalised multimedia content to explain genetic test results and consent processes to patients digitally. The platform which integrates with labs and healthcare providers automates parts of the counselling workflow, from scheduling tests to automatically generating reports.

Co-founder and CEO Dr Doron Behar says Igentifys platform can address the growing demand for clinical genetic testing: The demand for clinical genetic testing is skyrocketing. In todays market, we have over 27 million annual clinical genetic tests that are being done globally. But for all of these, we have only 7000 genetic counsellors available worldwide.

Behar explained that many people would prefer an automated video instead of a face-to-face appointment, due to waiting lists, and healthcare providers having a limited time for each patient. This is supported by data from Igentifys expanded carrier screen (ECS) study (NCT04248504).

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The ECS study evaluated the DGA in 225 couples undergoing ECS via the Thermo Fisher Scientific CarrierScan. Results demonstrated that the system saved traditional face-to-face or telephonic counselling in 73% of couples who were not carriers of a mutation in the same gene. Out of these, only 5.4% requested face-to-face counselling. In addition, patient survey responses showed that 90% of patients preferred digital results.

The AI genetic consultancy raised $10.5m in a 2019 funding round led by life sciences venture fund aMoon and crowdfunding platform OurCrowd. Founded in 2016, Igentify has partnered with companies such as Illumina and Thermo Fisher Scientific for its DGA.

AI is expected to drive the next industrial revolution, according to a report on GlobalDatas Medical Intelligence Center. Analysts estimate the total AI market will be worth $1tn by 2030, up from $103bn in 2023.

You simply dont have enough personnel to explain about the booming of knowledge in medicine to follow up on patients and so forth. We are here to pioneer and be part of this revolution, concluded Behar.

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Originally posted here:
How Igentify are revolutionising genetic testing using AI - Medical Device Network

Recommendation and review posted by Bethany Smith

A New York Times story this week about tennis legend Chris Everts battletwicewith ovarian cancer painted a simple and powerful picture: Fearing for her own risk after her sister died of the disease, Evert got tested, caught it early, as stage 1, and treated it successfully in 2022. And though it returnedstage 1 again, meaning it had not spreadshe was able to catch that, too, and treat it again. Now the 69-year-old has been declared cancer-free a second time.

As with her original diagnosis, the story notes, early testing was criticala message Ms. Evert shares zealously.

Except for just one problem: When it comes to ovarian cancer, there is no such thing as early testing.

There is no approved screening. There is no method of early detection, Sarah DeFeo, chief program officer at the Ovarian Cancer Research Alliance (OCRA), tells Fortune. Its a rare disease, with a one-in-87 over-lifetime risk, so its not something that happens as part of a well-woman checkup, whether with a gynecologist or regular internal medicine.

Thats because, says Dr. Gillian Hanley, a member of OCRAs scientific advisory committee and an associate professor of obstetrics and gynecology at the University of British Columbia, all of the screening methods that have been tried have failed to decrease mortality rates to date, which is how we determine whether or not a screening method is effective.

While there are some standard ways of surveilling for ovarian cancer if it is suspectedincluding a CA-125 blood test that could possibly indicate tumor markers and a transvaginal ultrasound that could help identify massesthey are imprecise. Plus, they are not indicated or available to women in the absence of either symptomswhich tend to only reveal themselves once the cancer has progressed significantlyor a high-risk factor, meaning the patient has already tested positive for carrying genetic markers that significantly raise the possibility of getting ovarian cancer.

If youre just a regular, average-risk person walking around in the world, a doctor may be like, [a routine scan is] not medically indicated. Theres no need for that Theres no evidence to suggest that ultrasounds are effective,' says DeFeo. So thats not something that is recommended. Its not neutral its like, No, dont do it.

Instead, what women should consider, she says, is getting tested for genetic markers. Its something Evert has talked about previouslyhaving tested positive for the BRCA-1 gene after her sisters death, then undergoing a preventative hysterectomy with removal of her ovaries and fallopian tubes. It was only then, through the pathology report, that she learned she had stage 1 ovarian cancer (which returned, even after the surgery, due to the fact that microscopic cancer cells can sometimes remain in the abdomen).

None of those details were mentioned in the most recent New York Times articlebut they are actually the most vital, says DeFeo.

She has talked a lot about getting tested early, but to me, the real story is about the importance of knowing your risk and about risk management, she says. I think that thats the important takeaway from her story.

Much of the current wisdom around screening comes out of the disappointing 2021 results of a U.K.-based clinical trial that followed 200,000 women for more than 20 years, concluding that screening and symptom awareness do not save lives.

The trial, which was the largest of its kind in the world, randomized patients into three groups: 1) no screening, 2) annual screening with ultrasound, and 3) annual screening with ultrasound and CA-125 blood test. It found no evidence of lives saved in the groups that were tested. We therefore cannot recommend ovarian cancer screening for the general population using these methods, lead investigator Dr. Usha Menon noted at the time.

This is whats tricky and devastating about ovarian cancer, that it needs to be caught so much earlier, we think, in order for it to impact mortality, says DeFeo. Its not about catching it three months earlier We need to find a way to catch this disease years earlier.

But as of now, thats not possible. The technology doesnt exist, she says. Plus, adds Hanley, most cases of ovarian cancer appear to originate in the fallopian tubeswhich are not easily reached or biopsied.

Its why OCRAs recommendation officially switched last year from symptom awareness and early detection to something else entirely: the preventative removal of ones fallopian tubes, called a salpingectomy. Its an approach that has been endorsed by the American College of Obstetricians and Gynecologists (ACOG) since 2015.

The recommendation applies not only to those who test positive for high genetic risk, such as with BRCA-1 or BRCA-2 gene mutations, but also for all women planning to undergo another pelvic surgery (such as with a hysterectomy, endometriosis, or removal of cysts) if they are finished or not planning on having kids. (For women with the higher risk, an oophorectomy, or prophylactic removal of ovaries, is also recommended.)

So again, were not saying that your regular woman on the street needs to go in and have this elective surgery, says DeFeo. But we know that hundreds of thousands of women are having surgery every year anyway, for a different reason, where they could take the opportunity to take out their tubes at the same time, potentially. Its something that they should talk to their doctor about, and its something that doctors should be thinking about.

Besides salpingectomy, the other most powerful tool in ovarian cancer prevention is genetic testing, which you can begin by looking at your family history. I know that in many families that can be hard, says DeFeo. But to the extent that you can look at your family history, and if you have a family history of cancer, especially breast and ovarian cancers, and especially at a young agethose are red flags.

Hanley adds that it is important to look at both sides of your family. There is a misconception that family history is only relevant on your mothers side, but you can inherit a BRCA mutation from your father as well, she says. So on either side of your family, if there is a history of breast or ovarian cancer, potentially even prostate or pancreatic cancers, then getting a BRCA test is a very good idea.

Then, talk to your doctor about getting it started.

DeFeo notes that genetic testing is more accessible than ever. A lot of insurance covers it. It really depends on each persons situation, but the cost of testing has come down dramatically over the course of the years, she says. So it is increasingly accessible. And OCRA, for example, offers a free genetic testing program.

From there, if you are positive, prophylactic surgeries would be recommended, as was the case with Evert.

She would never have been symptomatic, says Hanley. Theres no screening method that would have picked that up. The only reason that cancer was diagnosed is because her fallopian tubes were removed and then they were very, very carefully analyzed by a pathologistand that doesnt occur outside of the case of a BRCA mutation.

But Hanley, like others in the field, is counting on that to change. Were all hopeful that with technology and better understanding, we may still one day be able to develop a screening method that works, she says. But were a long way away from that.

More on cancer:

Read the rest here:
Ovarian cancer and Chris Evert: Why early detection doesn't help - Fortune

Recommendation and review posted by Bethany Smith

The global sequencing market size was valued at USD 15.59 billion in 2023 and is poised to grow from USD 19.05 billion in 2024 to hit around USD 115.85 billion by 2033, at a CAGR of 22.21% during the forecast period 2023- 2032.

The increasing demand for applications such as personalized medicine and genetic testing is expected to drive the growth of the sequencing market during the forecast period.

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Key Takeaways

The sequencing market is all about the technologies and services that allow us to read and understand the genetic code of living organisms. This involves identifying the order of DNA or RNA nucleotides, which are the building blocks of life. By doing this, scientists can learn a lot about how organisms' function, how diseases develop, and how we might treat them.

Sequencing Market at a Glance

The sequencing market is a rapidly expanding sector driven by the increasing application of DNA and RNA sequencing technologies across various fields. Sequencing is the process of determining the order of nucleotides in DNA or RNA, and it has become a fundamental tool in modern biology and medicine. With the advancements in technology, sequencing has become faster, more accurate, and more affordable, leading to its widespread adoption.

One of the main drivers of the sequencing market is its significant role in personalized medicine. By understanding an individual's genetic makeup, healthcare providers can tailor treatments to the specific needs of the patient, leading to more effective and targeted therapies. This is particularly important in the treatment of cancers, where sequencing can help identify the most appropriate drugs and treatment plans based on the genetic mutations present in the tumor.

Another important application of sequencing is in genetic testing. This allows individuals to learn about their ancestry, identify genetic disorders, and understand their risks for certain diseases.

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Emphasis on Personalized Medicine to Expand the Markets Growth

One of the most drivers of the sequencing market is the rise of personalized medicines. Next-generation sequencing (NSG) technology has revolutionized the way we understand and treat diseases by enabling the identification of genetic variations. These variations can influence a persons risk of developing certain diseases, how a disease progresses, and how an individual responds to treatment.

Personalized medicine aims to tailor medical treatment to the individual characteristics of each patient. By analyzing a patient's genetic profile, healthcare providers can develop more effective treatment plans that are specifically designed for that person.

A recent example of the impact of personalized medicine is the field of oncology. Cancer treatments have historically been based on the type and stage of cancer, but NGS has enabled a more nuanced approach. For instance, in 2023, a study highlighted how NGS was used to identify specific genetic mutations in patients with lung cancer. This allowed doctors to prescribe targeted therapies that were more effective than standard chemotherapy. As a result, patients experienced better outcomes, including higher survival rates and fewer side effects.

Rising Cancer Research to Boost the Markets Growth

Increasing cancer research is a significant driver of the sequencing market. Next generation sequencing (NGS) is an incredibly powerful tool that enables scientists to uncover the genetic mutations responsible for cancer development and progression. By providing details insights into the genetic landscape of cancer, NGS plays a crucial role in the fight against this complex disease.

One of the most important aspects of NGS in cancer research is its ability to identify specific genetic mutations that can drive cancer. These mutations often vary from patient to patient, making it challenging to develop universal treatment.

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Challenges with Data Analysis to Hamper the Markets Growth

One significant restraint on the growth of the sequencing market is the challenge of data analysis. Next-generation sequencing (NGS) produces vast amounts of data, which can be both a blessing and a curse. While this data is incredibly valuable, analyzing and interpreting it accurately requires advanced computational tools and expertise in bioinformatics. Unfortunately, the shortage of skilled personnel in this field can create a significant bottleneck for many institutions. NGS technology can sequence millions of DNA fragments in a single run, generating terabytes of data that need to be processed and analyzed. This data includes not just the sequences themselves but also information about genetic variations, mutations, and other anomalies.

A recent example highlighting this challenge is the COVID-19 pandemic. The rapid spread of the virus created an urgent need for genome sequencing to track mutations and understand the virus's evolution. Many countries ramped up their sequencing efforts, producing an unprecedented amount of genomic data.

Application in Non-human Fields to Offer Opportunities

In agriculture, next generation sequencing is playing a critical role in crop improvement. By sequencing the genomes of various plants, researchers can identify traits associated with higher yields, disease resistance, and environmental tolerance. For example, scientists have used NGS to develop drought-resistant corn varieties, ensuring food security in regions prone to water scarcity.

Animal breeding is another area where NGS is making significant strides. Traditionally, selective breeding relied on phenotypic traits, which could take generations to manifest. With NGS, breeders can now identify and select desirable genetic traits much faster. For instance, in dairy cattle, sequencing can help identify genes associated with higher milk production or disease resistance, leading to healthier herds and improved dairy yields.

Environmental science is also benefiting from the advancements in NGS. Researchers use this technology to monitor biodiversity, track the spread of invasive species, and understand ecological dynamics. A notable example is the use of environmental DNA (eDNA) sequencing to monitor aquatic ecosystems.

A recent example illustrating the growing application of NGS is the use of metagenomics in soil analysis. Researchers have begun using NGS to study the complex microbial communities in soil, which play a crucial role in nutrient cycling and plant health.

North America to Sustain as a Leader in the Market

North America has been a dominant force in the sequencing market, contributing to the largest revenue share in 2023. This region's leadership can be attributed to continuous technological advancements and significant investments in research and development. The United States and Canada, with their well-established healthcare infrastructures, are at the forefront of this growth. Notably, initiatives like the AMD program in the U.S. are enhancing capabilities by integrating next-generation sequencing tools in public health systems, thereby driving market expansion.

Asia Pacific to Grow on a Rapid Pace in the Sequencing Market

The Asia Pacific region is expected to witness the fastest growth in the sequencing market during the forecast period. Countries such as China, Japan, and India are at the center of this expansion. The presence of regional companies like BGI Genomics and the availability of NGS services from providers like First BASE Laboratories Sdn Bhd are driving market growth. In India, the "10,000 genomes" initiative by the Department of Biotechnology (DBT) aims to establish an Indian whole-genome sequencing reference database, highlighting the region's commitment to advancing genomic research.

India is a particularly noteworthy market within the Asia Pacific region. With its vast and genetically diverse population, India offers significant opportunities for genomic research. The conclusion of the "10,000 genomes" initiative is a major milestone, aiming to create a comprehensive reference database for whole-genome sequencing in India. Recent developments in India also include the establishment of advanced sequencing facilities and collaborations with global genomic companies.

By Product & Services, the Consumables to Lead the Market as a Major Segment

The consumables segment, which includes kits, reagents, and accessories, dominated the sequencing market in 2023. Consumables are essential for the sequencing process as they are used in every step, from sample preparation to the actual sequencing and data analysis. The high frequency of use and the need for constant replenishment make consumables a critical component, driving significant revenue.

By Workflow, the Sequencing Segment to Sustain its Dominance in the Upcoming Period

Within the workflow category, the sequencing segment held the largest revenue share in 2023. Sequencing involves the actual process of determining the order of nucleotides in DNA or RNA. Advances in sequencing technology have significantly reduced costs and increased speed and accuracy, making this segment the backbone of the entire genomic analysis process.

By Application, the Oncology Segment to Lead the Market

Oncology was the dominant application segment in 2023, reflecting the critical role of sequencing in cancer research and treatment. Sequencing technologies help identify genetic mutations and alterations that drive cancer, enabling personalized treatment plans and improving patient outcomes. The rising prevalence of cancer worldwide continues to boost the demand for sequencing in oncology.

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Continued here:
Sequencing Market Size to Rise at a Healthy 22.21% of CAGR to Reach USD 115.85 Billion by 2033 - BioSpace

Recommendation and review posted by Bethany Smith

Ocugen has dosed the first patient with retinitis pigmentosa (RP) in its phase 3liMeliGhTtrial (NCT06388200) of OCU400 gene therapy.1

Patients with RP associated with mutations in multiple genes currently have no therapeutic options. As a retinal surgeon, I am encouraged by the therapeutic potential of OCU400 to provide long-term benefit to RP patients, Lejla Vajzovic, MD, FASRS, Director, Duke Surgical Vitreoretinal Fellowship Program, Associate Professor of Ophthalmology with Tenure Adult and Pediatric Vitreoretinal Surgery and Disease, Duke University Eye Center, and Retina Scientific Advisory Board Chair, Ocugen, said in a statement.1 OCU400 is a novel modifier gene therapy approach that could initiate a paradigm shift in the treatment of RP and to field of ophthalmology.

The phase 3 trial will last 1 year and have a sample size of 150 participants, at least 8 years of age, half with RHO gene mutations and half that have gene agnostic RP. Each arm is randomized 2:1 to receive either 2.5 x 1010 vg/eye of OCU400 or control. The studys primary endpoint is achieving an improvement of at least 2 Lux levels from baseline in the study eyes on Luminance Dependent Navigation Assessment (LDNA). Ocugen announced that it had received investigational new drug application clearance for a phase 3 trial of OCU400 in April 2024.2

The current OCU400 Phase 3 study is very exciting and gives hope for thousands of individuals with RP, Benjamin Bakall, MD, PhD, Director, Clinical Research, Associated Retina Consultants (ARC) and Clinical Assistant Professor, University of Arizona, College of Medicine Phoenix, added.2 I am encouraged that we may have a potential treatment option to preserve or improve the vision in RP patients regardless of gene mutation, and very pleased that the first patient dosing in the Phase 3 liMeliGhT clinical trial was performed at ARC.

READ MORE: Multicharacteristic Opsin Gene Therapy Improves BCVA, MLSDT in Retinitis Pigmentosa

OCU400 has previously been evaluated in a phase 1/2 trial, data from which suggests positive trends in Best-Corrected Visual Acuity (BCVA) and Multi-Luminance Mobility Testing (MLMT), and Low-Luminance Visual Acuity (LLVA) among treated eyes. In this study, most patients (89%; n = 16/18) demonstrated preservation or improvement in the treated eye either on BCVA or LLVA or MLMT scores from baseline, and 80% (n = 8/10) ofpatients with an RHOmutation experienced either preservation or improvement in MLMT scores from baseline. Most (78%; n = 18) also had preservation or improvement in treated eyes in MLMT scores from baseline.

We are grateful for our continued collaboration with Dr. Bakall and the team at ARC, said Huma Qamar, MD, MPH, Chief Medical Officer, Ocugen, added.1 "We are excited to expand our enrollment to include more centers and patients representing a diverse array of RP gene mutations, which will be a validation of this novel gene therapy platform. We will provide updates as our progress continues."

Each clinical milestone achieved by OCU400 brings us closer to providing a one-time treatment for life to patients living with RP, Shankar Musunuri, PhD, MBA, Chairman, CEO and cofounder, Ocugen, added.1 Dosing the first patient is especially significant and makes our dedication to serving RP patients300,000 in the U.S. and Europe and 1.6 million worldwidemore tangible.

See the original post here:
Ocugen Doses First Patient With Retinitis Pigmentosa Gene Therapy in Phase 3 Trial - CGTLive

Recommendation and review posted by Bethany Smith

The development of drugs and gene therapies for rare diseases is costly. It requires significant investments in advanced technology, clinical trials, and regulatory approvals. But what happens when the development of such gene therapies is paused once they are no longer commercially viable?

A few weeks ago, Swiss biopharma Basilea announced it will sell and transfer all rights for the companys glioblastoma candidate lisavanbulin (BAL101553) to the Glioblastoma Foundation for an undisclosed initial purchase cost. The charitable organisation plans to take over lisavanbuilins post-access trial programme, allowing patients from previous clinical studies to continue receiving the drug.

Similarly, in April 2024, Great Ormond Street Hospital (GOSH) in the UK announced that it is attempting to obtain the licence for gene therapy simoladagene autotemcel to treat the rare disease adenosine deaminase-deficient severe combined immunodeficiency (ADA-SCiD) on a non-profit basis. This came after the University College London-spinout Orchard Therapeutics, which planned to bring it to market, dropped out of its development plans. If successful, this will be the first time that an NHS trust has the authorisation to market a drug for this kind of treatment.

ADA-SCiD is a rare genetic disorder marked by a severely deficient immune system due to mutations in the ADA gene, which is crucial for producing the enzyme adenosine deaminase. It causes a severely compromised immune system, leading to recurrent, severe infections, and developmental delays.

Across three clinical trials conducted in the US and UK, 50 patients with ADA-SCiD were treated with simoladagene autotemcel, which was co-developed by labs at UCL and University of California Los Angeles. The overall survival with the gene therapy was 100% in all studies up to 36 months. Event-free survival, defined as no need for enzyme-replacement therapy or rescue allogeneic haematopoietic stem-cell transplantation, reached 97% and 95% at 24 months, respectively, in the two US studies (NCT01852071 and NCT02999984) and 95% in the UK study (NCT01380990).

The gene therapy is currently available to patients in clinical trials, but it is important for these therapies to be approved. Dr. Claire Booth, who leads the ADA-SCiD clinical trial at GOSH, says We want to ensure that these proven treatments can be offered to patients and families quickly and simply, without the need to look at compassionate use approaches.

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One of the main challenges associated with developing gene therapies is funding. It is difficult to get funding from venture capital or private investors due to small patient populations and uncertain returns. Grants can fund early clinical trials, but not the full development and approval process, which requires more funding, explains Dr. Donald Kohn, lead investigator of the ADA-SCiD programme at UCLA, and Distinguished Professor, Microbiology, Immunology and Molecular Genetics.

Another huge challenge is the expensive commercial-grade manufacturing costs. Commercial feasibility plays a big role in pharma companies progressing drug development and this may be challenging in ultra-rare diseases with small patient populations. Advanced therapies like gene therapy are costly and complex to produce.

Simoladagene autotemcel is composed of autologous CD34+ haematopoietic stem and progenitor cells (HSPCs) transduced ex vivo with a self-inactivating lentiviral vector encoding human ADA. Lentiviral vector production represents a large portion of the high costs associated with such therapies.

The cost of reagents needed to make a gene therapy product is high, but we hope that this may come down in the future, says Booth.

One company that is trying to tackle high manufacturing costs is Ori Biotech. The biotech, which is headquartered in London, UK and Woodcliff, New Jersey, has developed an automated platform that streamlines the cell therapy manufacturing process.

[Oris] IRO platform takes the most labour-intensive and time-consuming parts: activation, transduction, expansion, and harvest, and automates them into one integrated system without any manual interventions or tubing, said Ori Biotechs CEO Jason Foster.

In doing so, the platform aims to increase throughput, lower cost, and improve reliability by reducing failure rates. Ori has worked with companies like North Carolina-based Inceptor Bio to scale up manufacturing of their chimeric antigen receptor (CAR)-M, CAR-T and CAR-NK programmes. One of its candidates IB-T101 is set to enter clinical trials in Q4 2024.

In addition to funding challenges and manufacturing costs, there might also be differences based on locations in how gene therapies are made accessible to patients, says Kohn. He explained that national healthcare systems, like those in Europe, may have some advantage in funding rare disease gene therapies compared to the US healthcare system that includes multiple private payers. With a single national payer, developers only need to negotiate reimbursement with one entity rather than many private insurers. Additionally, Kohn said national systems can recognise that an initially high-cost therapy might save money over many years if it treats a fatal or chronic rare disease.

Just as a nonprofit hospital like GOSH is attempting to license EFS-ADA, there are other cases of individuals taking matters into their own hands, via an untraditional route. Terry Pirovolakis started Elpida Therapeutics, a not-for-profit biotech, after his son Michael was diagnosed with a rare disease called spastic paraplegia type 50 (SPG50) at five months old.

After Michael received his diagnosis, Pirovolakis said: We were told, Go home, love him. Theres not much we can do. Hell be paralysed from the waist down by the age of 10, quadriplegic by the age of 20. I just couldnt accept that fate for my child.

Elpida, which is set up as a company but operates as a nonprofit, was initially funded with money from philanthropists. Pirovolakis explained that the model works through partnerships with companies, institutions, and hospitals. When the organisation partners with a hospital, the latter agrees to treat a certain number of patients for free, or at a very low cost. In exchange, Elpida gives the hospital a promissory note.

He explains that funds through incentives from the US Food and Drug Administration (FDA) like priority review vouchers (PRV) for a gene therapy product will be used to pay the hospitals, and to hopefully fund more programmes.

Theyre [the hospital] taking on a mutual risk with us knowing that were trying to do good, not just trying to make money, said Pirovolakis.

Elpida aims to use any money it makes after paying the promissory notes to fund more programmes. Earlier this month, Pirovolakis mentioned that the FDA greenlit Elpidas plans to initiate a Phase III study of its lead candidate Melpida for patients with the rare disorder SPG50. Eight children will be dosed in the trial that is set to begin in August 2024. This is off the back of an ongoing Phase I/II (NCT05518188) trial.

Pirovolakis says there can be a socially acceptable way of dealing with the therapies once theyre deemed commercially unviable. Pharma companies want to help find therapies for rare diseases but also need to consider their best interests. So, when they drop it [a therapy], [giving it] to another company, or back to the university.thats an ethical way of doing things.

When they hold it for five or 10 years, looking for a financial partner to recoup their lost assets, that is not the right way of doing things.

Despite the promise of these alternate models, Pirovolakis delivers a stark reminder: Our model isnt ideal; it is out of necessity.

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Left in limbo: When pharma halts rare disease research - Pharmaceutical Technology

Recommendation and review posted by Bethany Smith

Fort Lauderdale, FL, July 02, 2024 (GLOBE NEWSWIRE) -- Move over, lotions and serums: taking a skin care supplement is an increasingly popular way to support healthy, youthful-looking skin. A recent survey of over 3,000 Life Extension customers* revealed that the top two skin care supplements are vitamin C, with 70% of respondents taking it, while 53% choose traditional collagen supplements. For those who would prefer a vegan alternative to collagen, Life Extension has launched Vegan Pro Collagen. This innovative formula delivers a clinically studied combination of amino acids, vitamin C and botanical extracts to aid collagen production in the body, and in clinical studies has been shown to help reduce the appearance of wrinkles by 14%, enhance skin texture by 13% and increase collagen density by 8% after just eight weeks of use. *Life Extension Customer Survey conducted May 2024

Our ingredients include a carefully curated blend of collagen-friendly vitamin C, gotu kola and ginseng root extracts, as well as the identical amino acid building blocks as type I collagen, which the body can use to make new collagen. This product was developed in collaboration with a skin tissue expert, Dr. Josu Jimnez Vzquez, PhD (National Polytechnic Institute, Mexico), whose research led to the formulation of the first science-based vegan alternative to type I animal collagen supplements, explained Life Extensions Innovation Team Leader, Dr. Asha Jaja-Chimedza, PhD.

According to Michael A. Smith, MD, Life Extensions Director of Education, there are no vegan sources of collagen, but there are foods and ingredients that encourage normal collagen production in the body like tofu, lentils, citrus fruits, gotu kola and ginseng root. If you follow vegan or vegetarian dietary patterns, or dont care for traditional collagen supplements, finding an alternative that delivers collagen-friendly nutrients as well as an identical amino acid profile is a proactive way to keep youthful-looking skin, he added.

Vegan Pro Collagen is the newest addition to Life Extensions skin health line. It includes Skin Care Collection Day and Night Creams, topical lotions that support against signs of aging, and Daily Skin Defense, an oral supplement that locks in moisture and helps minimize the appearance of wrinkles and fine lines.

About Life Extension For more than 40 years, Life Extension has pursued innovative advances in health, conducting rigorous clinical trials and setting some of the most demanding standards in the industry to offer a full range of quality vitamins and nutritional supplements and blood-testing services. Life Extensions Wellness Specialists provide personalized counsel to help customers choose the right products for optimal health,nutritionand personal care. To learn more, visit LifeExtension.com.

These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure, or prevent any disease.

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Oral Skin Care Supplements an Increasingly Popular Option to Fight Signs of Aging - GlobeNewswire

Recommendation and review posted by Bethany Smith

Prosperity Consulting Group LLC purchased a new position in CRISPR Therapeutics AG (NASDAQ:CRSP Free Report) during the 1st quarter, according to its most recent Form 13F filing with the Securities and Exchange Commission (SEC). The firm purchased 2,966 shares of the companys stock, valued at approximately $202,000.

Several other large investors also recently bought and sold shares of the business. ARK Investment Management LLC boosted its holdings in shares of CRISPR Therapeutics by 19.2% during the 4th quarter. ARK Investment Management LLC now owns 8,536,104 shares of the companys stock worth $534,360,000 after purchasing an additional 1,372,986 shares during the last quarter. Norges Bank acquired a new position in CRISPR Therapeutics during the fourth quarter worth $38,661,000. Vestmark Advisory Solutions Inc. acquired a new position in CRISPR Therapeutics during the fourth quarter worth $10,848,000. PBCay One RSC Ltd purchased a new stake in CRISPR Therapeutics in the 4th quarter valued at $10,329,000. Finally, Trexquant Investment LP acquired a new stake in shares of CRISPR Therapeutics in the 4th quarter worth $8,287,000. Hedge funds and other institutional investors own 69.20% of the companys stock.

A number of brokerages recently issued reports on CRSP. Cantor Fitzgerald reissued a neutral rating on shares of CRISPR Therapeutics in a report on Thursday, May 9th. Piper Sandler restated an overweight rating and set a $105.00 price target on shares of CRISPR Therapeutics in a report on Monday, June 17th. Wells Fargo & Company decreased their price objective on CRISPR Therapeutics from $70.00 to $65.00 and set an equal weight rating on the stock in a report on Thursday, May 9th. JMP Securities reissued a market outperform rating and set a $86.00 target price on shares of CRISPR Therapeutics in a research note on Thursday, May 9th. Finally, Robert W. Baird lifted their target price on CRISPR Therapeutics from $46.00 to $52.00 and gave the company a neutral rating in a research report on Thursday, May 9th. Three research analysts have rated the stock with a sell rating, eight have issued a hold rating and eight have assigned a buy rating to the company. According to data from MarketBeat, the company currently has a consensus rating of Hold and an average price target of $75.71.

In other news, COO Julianne Bruno sold 3,366 shares of the businesss stock in a transaction dated Friday, June 21st. The stock was sold at an average price of $56.09, for a total value of $188,798.94. Following the completion of the sale, the chief operating officer now directly owns 6,745 shares of the companys stock, valued at approximately $378,327.05. The transaction was disclosed in a document filed with the Securities & Exchange Commission, which can be accessed through the SEC website. In other news, COO Julianne Bruno sold 3,366 shares of the firms stock in a transaction that occurred on Friday, June 21st. The shares were sold at an average price of $56.09, for a total transaction of $188,798.94. Following the transaction, the chief operating officer now directly owns 6,745 shares in the company, valued at $378,327.05. The sale was disclosed in a legal filing with the SEC, which is accessible through this hyperlink. Also, CEO Samarth Kulkarni sold 19,582 shares of the companys stock in a transaction on Monday, April 15th. The shares were sold at an average price of $59.91, for a total transaction of $1,173,157.62. Following the completion of the sale, the chief executive officer now owns 208,122 shares of the companys stock, valued at approximately $12,468,589.02. The disclosure for this sale can be found here. 4.10% of the stock is currently owned by insiders.

CRSP stock opened at $53.10 on Friday. The business has a 50 day moving average price of $56.57 and a 200 day moving average price of $64.18. The stock has a market cap of $4.51 billion, a price-to-earnings ratio of -19.52 and a beta of 1.70. CRISPR Therapeutics AG has a fifty-two week low of $37.55 and a fifty-two week high of $91.10.

CRISPR Therapeutics (NASDAQ:CRSP Get Free Report) last issued its quarterly earnings data on Wednesday, May 8th. The company reported ($1.43) earnings per share for the quarter, missing the consensus estimate of ($1.35) by ($0.08). The firm had revenue of $0.50 million for the quarter, compared to analyst estimates of $25.53 million. The companys revenue was down 99.5% on a year-over-year basis. During the same period in the previous year, the company earned ($0.67) EPS. As a group, sell-side analysts anticipate that CRISPR Therapeutics AG will post -5.51 EPS for the current year.

(Free Report)

CRISPR Therapeutics is a gene-editing company focused on developing transformative gene-based medicines for serious diseases using its proprietary CRISPR/Cas9 platform. CRISPR/Cas9 is a revolutionary gene-editing technology that allows for precise, directed changes to genomic DNA. CRISPR Therapeutics has established a portfolio of therapeutic programs across a broad range of disease areas including hemoglobinopathies, oncology, regenerative medicine and rare diseases.

Want to see what other hedge funds are holding CRSP? Visit HoldingsChannel.com to get the latest 13F filings and insider trades for CRISPR Therapeutics AG (NASDAQ:CRSP Free Report).

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Prosperity Consulting Group LLC Invests $202000 in CRISPR Therapeutics AG (NASDAQ:CRSP) - Defense World

Recommendation and review posted by Bethany Smith

Doudna, J. A. The promise and challenge of therapeutic genome editing. Nature 578, 229236 (2020).

Article CAS PubMed PubMed Central Google Scholar

Raguram, A., Banskota, S. & Liu, D. R. Therapeutic in vivo delivery of gene editing agents. Cell 185, 28062827 (2022).

Article CAS PubMed PubMed Central Google Scholar

Wang, D., Zhang, F. & Gao, G. CRISPR-based therapeutic genome editing: strategies and in vivo delivery by AAV vectors. Cell 181, 136150 (2020).

Article CAS PubMed PubMed Central Google Scholar

Kim, D., Luk, K., Wolfe, S. A. & Kim, J.-S. Evaluating and enhancing target specificity of gene-editing nucleases and deaminases. Annu. Rev. Biochem. 88, 191220 (2019).

Article CAS PubMed Google Scholar

Tao, J., Bauer, D. E. & Chiarle, R. Assessing and advancing the safety of CRISPRCas tools: from DNA to RNA editing. Nat. Commun. 14, 212 (2023).

Article CAS PubMed PubMed Central Google Scholar

Kim, D. et al. Digenome-seq: genome-wide profiling of CRISPRCas9 off-target effects in human cells. Nat. Methods 12, 237243 (2015).

Article CAS PubMed Google Scholar

Cameron, P. et al. Mapping the genomic landscape of CRISPRCas9 cleavage. Nat. Methods 14, 600606 (2017).

Article CAS PubMed Google Scholar

Tsai, S. Q. et al. CIRCLE-seq: a highly sensitive in vitro screen for genome-wide CRISPRCas9 nuclease off-targets. Nat. Methods 14, 607614 (2017).

Article CAS PubMed PubMed Central Google Scholar

Tsai, S. Q. et al. GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPRCas nucleases. Nat. Biotechnol. 33, 187197 (2015).

Article CAS PubMed Google Scholar

Wienert, B. et al. Unbiased detection of CRISPR off-targets in vivo using DISCOVER-Seq. Science 364, 286289 (2019).

Article CAS PubMed PubMed Central Google Scholar

Zou, R. S. et al. Improving the sensitivity of in vivo CRISPR off-target detection with DISCOVER-Seq+. Nat. Methods 20, 706713 (2023).

Urnov, F. D., Rebar, E. J., Holmes, M. C., Zhang, H. S. & Gregory, P. D. Genome editing with engineered zinc finger nucleases. Nat. Rev. Genet. 11, 636646 (2010).

Article CAS PubMed Google Scholar

Joung, J. K. & Sander, J. D. TALENs: a widely applicable technology for targeted genome editing. Nat. Rev. Mol. Cell Biol. 14, 4955 (2013).

Article CAS PubMed Google Scholar

Cong, L. et al. Multiplex genome engineering using CRISPR/Cas systems. Science 339, 819823 (2013).

Article CAS PubMed PubMed Central Google Scholar

Anzalone, A. V., Koblan, L. W. & Liu, D. R. Genome editing with CRISPRCas nucleases, base editors, transposases and prime editors. Nat. Biotechnol. 38, 824844 (2020).

Article CAS PubMed Google Scholar

Komor, A. C., Kim, Y. B., Packer, M. S., Zuris, J. A. & Liu, D. R. Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Nature 533, 420424 (2016).

Article CAS PubMed PubMed Central Google Scholar

Anzalone, A. V. et al. Search-and-replace genome editing without double-strand breaks or donor DNA. Nature 576, 149157 (2019).

Article CAS PubMed PubMed Central Google Scholar

Gaudelli, N. M. et al. Programmable base editing of AT to GC in genomic DNA without DNA cleavage. Nature 551, 464471 (2017).

Article CAS PubMed PubMed Central Google Scholar

Liu, T. & Huang, J. Replication protein A and more: single-stranded DNA-binding proteins in eukaryotic cells. Acta Biochim Biophys. Sin. 48, 665670 (2016).

Article CAS PubMed Google Scholar

Wold, M. S. Replication protein A: a heterotrimeric, single-stranded DNA-binding protein required for eukaryotic DNA metabolism. Annu. Rev. Biochem. 66, 6192 (1997).

Article CAS PubMed Google Scholar

Skene, P. J., Henikoff, J. G. & Henikoff, S. Targeted in situ genome-wide profiling with high efficiency for low cell numbers. Nat. Protoc. 13, 10061019 (2018).

Article CAS PubMed Google Scholar

Kabeche, L., Nguyen, H., Buisson, R. & Zou, L. A mitosis-specific and R loop-driven ATR pathway promotes faithful chromosome segregation. Science 359, 108114 (2018).

Gan, X. et al. Proper RPA acetylation promotes accurate DNA replication and repair. Nucleic Acids Res. 51, 55655583 (2023).

Article CAS PubMed PubMed Central Google Scholar

Amemiya, H. M., Kundaje, A. & Boyle, A. P. The ENCODE blacklist: identification of problematic regions of the genome. Sci. Rep. 9, 9354 (2019).

Article PubMed PubMed Central Google Scholar

Ferrari, M., Twayana, S., Marini, F. & Pellicioli, A. In Genome Instability: Methods and Protocols (eds Muzi-Falconi, M. & Brown, G. W.) 119129 (Humana Press, 2017).

Stoler, N. & Nekrutenko, A. Sequencing error profiles of Illumina sequencing instruments. NAR Genom. Bioinform. 3, lqab019 (2021).

Article PubMed PubMed Central Google Scholar

Kim, D., Kim, S., Kim, S., Park, J. & Kim, J.-S. Genome-wide target specificities of CRISPRCas9 nucleases revealed by multiplex Digenome-seq. Genome Res. 26, 406415 (2016).

Article CAS PubMed PubMed Central Google Scholar

Lei, Z. et al. Detect-seq reveals out-of-protospacer editing and target-strand editing by cytosine base editors. Nat. Methods 18, 643651 (2021).

Article CAS PubMed Google Scholar

Liang, P. et al. Genome-wide profiling of adenine base editor specificity by EndoV-seq. Nat. Commun. 10, 67 (2019).

Article CAS PubMed PubMed Central Google Scholar

Liang, S.-Q. et al. Genome-wide profiling of prime editor off-target sites in vitro and in vivo using PE-tag. Nat. Methods 20, 898907 (2023).

Article CAS PubMed Google Scholar

Kim, D. Y., Moon, S. B., Ko, J.-H., Kim, Y.-S. & Kim, D. Unbiased investigation of specificities of prime editing systems in human cells. Nucleic Acids Res. 48, 1057610589 (2020).

Article CAS PubMed PubMed Central Google Scholar

Zuo, E. et al. Cytosine base editor generates substantial off-target single-nucleotide variants in mouse embryos. Science 364, 289292 (2019).

Article CAS PubMed PubMed Central Google Scholar

Duan, J. et al. Genome-wide identification of CRISPR/Cas9 off-targets in human genome. Cell Res. 24, 10091012 (2014).

Article CAS PubMed PubMed Central Google Scholar

Frangoul, H. et al. CRISPRCas9 gene editing for sickle cell disease and -thalassemia. N. Engl. J. Med. 384, 252260 (2021).

Article CAS PubMed Google Scholar

Nakamura-Ishizu, A., Takizawa, H. & Suda, T. The analysis, roles and regulation of quiescence in hematopoietic stem cells. Development 141, 46564666 (2014).

Article CAS PubMed Google Scholar

Chang, H. H. Y., Pannunzio, N. R., Adachi, N. & Lieber, M. R. Non-homologous DNA end joining and alternative pathways to double-strand break repair. Nat. Rev. Mol. Cell Biol. 18, 495506 (2017).

Article CAS PubMed PubMed Central Google Scholar

Wienert, B., Wyman, S. K., Yeh, C. D., Conklin, B. R. & Corn, J. E. CRISPR off-target detection with DISCOVER-seq. Nat. Protoc. 15, 17751799 (2020).

Article CAS PubMed PubMed Central Google Scholar

Wheeler, D. L. et al. Database resources of the National Center for Biotechnology Information. Nucleic Acids Res. 33, D39D45 (2005).

Article CAS PubMed Google Scholar

Zhang, H. et al. Fast alignment and preprocessing of chromatin profiles with Chromap. Nat. Commun. 12, 6566 (2021).

Article CAS PubMed PubMed Central Google Scholar

Quinlan, A. R. & Hall, I. M. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26, 841842 (2010).

Article CAS PubMed PubMed Central Google Scholar

Kent, W. J., Zweig, A. S., Barber, G., Hinrichs, A. S. & Karolchik, D. BigWig and BigBed: enabling browsing of large distributed datasets. Bioinformatics 26, 22042207 (2010).

Article CAS PubMed PubMed Central Google Scholar

Ramirez, F. et al. deepTools2: a next generation web server for deep-sequencing data analysis. Nucleic Acids Res. 44, W160W165 (2016).

Article CAS PubMed PubMed Central Google Scholar

Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357359 (2012).

Article CAS PubMed PubMed Central Google Scholar

Danecek, P. et al. Twelve years of SAMtools and BCFtools. GigaScience 10, giab008 (2021).

Article PubMed PubMed Central Google Scholar

Bleckwehl, T. et al. Enhancer-associated H3K4 methylation safeguards in vitro germline competence. Nat. Commun. 12, 5771 (2021).

Article CAS PubMed PubMed Central Google Scholar

Man, N. et al. p300 suppresses the transition of myelodysplastic syndromes to acute myeloid leukemia. JCI Insight 6, e138478 (2021).

Article PubMed PubMed Central Google Scholar

Ji, L. et al. TOPORS, a tumor suppressor protein, contributes to the maintenance of higher-order chromatin architecture. Biochim. Biophys. Acta Gene Regul. Mech. 1863, 194518 (2020).

Article CAS PubMed Google Scholar

Lex, R. K. et al. GLI transcriptional repression regulates tissue-specific enhancer activity in response to Hedgehog signaling. eLife 9, e50670 (2020).

Article CAS PubMed PubMed Central Google Scholar

Boix, C. A., James, B. T., Park, Y. P., Meuleman, W. & Kellis, M. Regulatory genomic circuitry of human disease loci by integrative epigenomics. Nature 590, 300307 (2021).

Article CAS PubMed PubMed Central Google Scholar

Clement, K. et al. CRISPResso2 provides accurate and rapid genome editing sequence analysis. Nat. Biotechnol. 37, 224226 (2019).

Article CAS PubMed PubMed Central Google Scholar

Zhu, M. et al. Tracking-seq reveals the heterogeneity of off-target effects in CRISPR/Cas9-mediated genome editing. NCBI https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE236360 (2024).

Xu, R. Offtracker. GitHub https://github.com/Lan-lab/offtracker (2024).

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Recommendation and review posted by Bethany Smith

Davis, J. T. G-Quartets 40 years later: from 5-GMP to molecular biology and supramolecular chemistry. Angew. Chem. Int. Ed. Engl. 43, 668698 (2004).

Article CAS PubMed Google Scholar

Varshney, D., Spiegel, J., Zyner, K., Tannahill, D. & Balasubramanian, S. The regulation and functions of DNA and RNA G-quadruplexes. Nat. Rev. Mol. Cell Biol. 21, 459474 (2020).

Article CAS PubMed PubMed Central Google Scholar

Kosiol, N., Juranek, S., Brossart, P., Heine, A. & Paeschke, K. G-Quadruplexes: a promising target for cancer therapy. Mol. Cancer 20, 40 (2021).

Article CAS PubMed PubMed Central Google Scholar

Qin, H., Zhao, C., Sun, Y., Ren, J. & Qu, X. Metallo-supramolecular complexes enantioselectively eradicate cancer stem cells in vivo. J. Am. Chem. Soc. 139, 1620116209 (2017).

Article CAS PubMed Google Scholar

Meier-Stephenson, V. G4-Quadruplex-binding proteins: review and insights into selectivity. Biophys. Rev. 14, 635654 (2022).

Article CAS PubMed PubMed Central Google Scholar

Lejault, P., Mitteaux, J., Sperti, F. R. & Monchaud, D. How to untie G-quadruplex knots and why? Cell Chem. Biol. 28, 436455 (2021).

Article CAS PubMed Google Scholar

Santos, T., Salgado, G. F., Cabrita, E. J. & Cruz, C. Nucleolin: a binding partner of G-quadruplex structures. Trends Cell Biol. 32, 561564 (2022).

Article CAS PubMed Google Scholar

Roychoudhury, S. et al. Endogenous oxidized DNA bases and APE1 regulate the formation of G-quadruplex structures in the genome. Proc. Natl Acad. Sci. USA 117, 1140911420 (2020).

Article CAS PubMed PubMed Central Google Scholar

Mendoza, O., Bourdoncle, A., Boule, J. B., Brosh, R. M. Jr. & Mergny, J. L. G-Quadruplexes and helicases. Nucleic Acids Res. 44, 19892006 (2016).

Article CAS PubMed PubMed Central Google Scholar

Chen, M. C. et al. Structural basis of G-quadruplex unfolding by the DEAH/RHA helicase DHX36. Nature 558, 465469 (2018).

Article CAS PubMed PubMed Central Google Scholar

Rodriguez, R. et al. A novel small molecule that alters shelterin integrity and triggers a DNA-damage response at telomeres. J. Am. Chem. Soc. 130, 1575815759 (2008).

Article CAS PubMed PubMed Central Google Scholar

Liu, L. Y., Ma, T. Z., Zeng, Y. L., Liu, W. & Mao, Z. W. Structural basis of pyridostatin and its derivatives specifically binding to G-quadruplexes. J. Am. Chem. Soc. 144, 1187811887 (2022).

Article CAS PubMed Google Scholar

Verga, D., Hamon, F., Poyer, F., Bombard, S. & Teulade-Fichou, M. P. Photo-cross-linking probes for trapping G-quadruplex DNA. Angew. Chem. Int. Ed. Engl. 53, 994998 (2014).

Article CAS PubMed Google Scholar

Masson, T. et al. BrdU immuno-tagged G-quadruplex ligands: a new ligand-guided immunofluorescence approach for tracking G-quadruplexes in cells. Nucleic Acids Res. 49, 1264412660 (2021).

Article CAS PubMed PubMed Central Google Scholar

De Cian, A., Delemos, E., Mergny, J. L., Teulade-Fichou, M. P. & Monchaud, D. Highly efficient G-quadruplex recognition by bisquinolinium compounds. J. Am. Chem. Soc. 129, 18561857 (2007).

Article PubMed Google Scholar

Lemarteleur, T. et al. Stabilization of the c-myc gene promoter quadruplex by specific ligands inhibitors of telomerase. Biochem. Biophys. Res. Commun. 323, 802808 (2004).

Article CAS PubMed Google Scholar

Konermann, S. et al. Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex. Nature 517, 583588 (2015).

Article CAS PubMed Google Scholar

Chiarella, A. M. et al. Dose-dependent activation of gene expression is achieved using CRISPR and small molecules that recruit endogenous chromatin machinery. Nat. Biotechnol. 38, 5055 (2020).

Article CAS PubMed Google Scholar

Qin, G., Yang, J., Zhao, C., Ren, J. & Qu, X. Manipulating complex chromatin folding via CRISPR-guided bioorthogonal chemistry. Proc. Natl Acad. Sci. USA 119, e2204725119 (2022).

Article CAS PubMed PubMed Central Google Scholar

Wang, C. et al. dCas9-based gene editing for cleavage-free genomic knock-in of long sequences. Nat. Cell Biol. 24, 268278 (2022).

Article CAS PubMed PubMed Central Google Scholar

Siddiqui-Jain, A., Grand, C. L., Bearss, D. J. & Hurley, L. H. Direct evidence for a G-quadruplex in a promoter region and its targeting with a small molecule to repress c-MYC transcription. Proc. Natl Acad. Sci. USA 99, 1159311598 (2002).

Article CAS PubMed PubMed Central Google Scholar

Hui, W. W. I., Simeone, A., Zyner, K. G., Tannahill, D. & Balasubramanian, S. Single-cell mapping of DNA G-quadruplex structures in human cancer cells. Sci. Rep. 11, 23641 (2021).

Article CAS PubMed PubMed Central Google Scholar

Yu, Z. et al. Chem-map profiles drug binding to chromatin in cells. Nat. Biotechnol. 41, 12651271 (2023).

Article CAS PubMed PubMed Central Google Scholar

Shen, J. et al. Promoter G-quadruplex folding precedes transcription and is controlled by chromatin. Genome Biol. 22, 143 (2021).

Article PubMed PubMed Central Google Scholar

Hansel-Hertsch, R. et al. G-Quadruplex structures mark human regulatory chromatin. Nat. Genet. 48, 12671272 (2016).

Article CAS PubMed Google Scholar

Bian, W. X. et al. Binding of cellular nucleolin with the viral core RNA G-quadruplex structure suppresses HCV replication. Nucleic Acids Res. 47, 5668 (2019).

Article CAS PubMed Google Scholar

Li, C. et al. Ligand-induced native G-quadruplex stabilization impairs transcription initiation. Genome Res. 31, 15461560 (2021).

Article PubMed PubMed Central Google Scholar

Bochman, M. L., Paeschke, K. & Zakian, V. A. DNA secondary structures: stability and function of G-quadruplex structures. Nat. Rev. Genet. 13, 770780 (2012).

Article CAS PubMed PubMed Central Google Scholar

Lago, S., Tosoni, E., Nadai, M., Palumbo, M. & Richter, S. N. The cellular protein nucleolin preferentially binds long-looped G-quadruplex nucleic acids. Biochim. Biophys. Acta Gen. Subj. 1861, 13711381 (2017).

Article CAS PubMed Google Scholar

Weintraub, H. et al. The myoD gene family: nodal point during specification of the muscle cell lineage. Science 251, 761766 (1991).

Article CAS PubMed Google Scholar

Shklover, J., Weisman-Shomer, P., Yafe, A. & Fry, M. Quadruplex structures of muscle gene promoter sequences enhance in vivo MyoD-dependent gene expression. Nucleic Acids Res. 38, 23692377 (2010).

Article CAS PubMed PubMed Central Google Scholar

Yafe, A., Etzioni, S., Weisman-Shomer, P. & Fry, M. Formation and properties of hairpin and tetraplex structures of guanine-rich regulatory sequences of muscle-specific genes. Nucleic Acids Res. 33, 28872900 (2005).

Article CAS PubMed PubMed Central Google Scholar

McClure, M. J. et al. Role of integrin 71 signaling in myoblast differentiation on aligned polydioxanone scaffolds. Acta Biomater. 39, 4454 (2016).

Article CAS PubMed Google Scholar

Qin, G. et al. Unlocking G-quadruplexes as targets and tools against COVID-19. Chin. J. Chem. 41, 560568 (2023).

Abiri, A. et al. Unlocking G-quadruplexes as antiviral targets. Pharmacol. Rev. 73, 897923 (2021).

Article CAS PubMed Google Scholar

Neidle, S. Quadruplex nucleic acids as novel therapeutic targets. J. Med. Chem. 59, 59876011 (2016).

Article CAS PubMed Google Scholar

Renaud de la Faverie, A. et al. Nucleic acids targeted to drugs: SELEX against a quadruplex ligand. Biochimie 93, 13571367 (2011).

Article CAS PubMed Google Scholar

Gu, B., Posfai, E. & Rossant, J. Efficient generation of targeted large insertions by microinjection into two-cell-stage mouse embryos. Nat. Biotechnol. 36, 632637 (2018).

Article CAS PubMed Google Scholar

Di Antonio, M. et al. Single-molecule visualization of DNA G-quadruplex formation in live cells. Nat. Chem. 12, 832837 (2020).

Article PubMed PubMed Central Google Scholar

Tanenbaum, M. E., Gilbert, L. A., Qi, L. S., Weissman, J. S. & Vale, R. D. A protein-tagging system for signal amplification in gene expression and fluorescence imaging. Cell 159, 635646 (2014).

Article CAS PubMed PubMed Central Google Scholar

Morita, S. et al. Targeted DNA demethylation in vivo using dCas9-peptide repeat and scFv-TET1 catalytic domain fusions. Nat. Biotechnol. 34, 10601065 (2016).

Article CAS PubMed Google Scholar

Burger, A. M. et al. The G-quadruplex-interactive molecule BRACO-19 inhibits tumor growth, consistent with telomere targeting and interference with telomerase function. Cancer Res. 65, 14891496 (2005).

Article CAS PubMed Google Scholar

Kim, M. Y., Gleason-Guzman, M., Izbicka, E., Nishioka, D. & Hurley, L. H. The different biological effects of telomestatin and TMPyP4 can be attributed to their selectivity for interaction with intramolecular or intermolecular G-quadruplex structures. Cancer Res. 63, 32473256 (2003).

CAS PubMed Google Scholar

Hu, M. H., Lin, J. H. & Huang, Q. Discovery of a fluorescent, long chain-bridged bispurine that selectively targets the c-MYC G-quadruplex. Bioorg. Chem. 122, 105750 (2022).

Article CAS PubMed Google Scholar

Chambers, V. S. et al. High-throughput sequencing of DNA G-quadruplex structures in the human genome. Nat. Biotechnol. 33, 877881 (2015).

Article CAS PubMed Google Scholar

Yang, W. S. et al. Regulation of ferroptotic cancer cell death by GPX4. Cell 156, 317331 (2014).

Article CAS PubMed PubMed Central Google Scholar

Venugopal, R. & Jaiswal, A. K. Nrf2 and Nrf1 in association with Jun proteins regulate antioxidant response element-mediated expression and coordinated induction of genes encoding detoxifying enzymes. Oncogene 17, 31453156 (1998).

Article CAS PubMed Google Scholar

Maxwell, P. H. et al. The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 399, 271275 (1999).

Article CAS PubMed Google Scholar

Chen, J. et al. Expression of Q227L-Gs in MCF-7 human breast cancer cells inhibits tumorigenesis. Proc. Natl Acad. Sci. USA 95, 26482652 (1998).

Article CAS PubMed PubMed Central Google Scholar

West, J. A. et al. The long noncoding RNAs NEAT1 and MALAT1 bind active chromatin sites. Mol. cell 55, 791802 (2014).

Article CAS PubMed PubMed Central Google Scholar

Robinson, J., Raguseo, F., Nuccio, S. P., Liano, D. & Di Antonio, M. DNA G-quadruplex structures: more than simple roadblocks to transcription? Nucleic Acids Res. 49, 84198431 (2021).

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Mice

All mice were housed at the China Agricultural University Laboratory Animals Resource Center, where they were subjected to a standard lightdark cycle of 12h each, and maintained at a temperature of 2022C. All animal experiments were conducted in Sen Wus laboratory and were approved by the Institutional Animal Care and Use Committee of China Agricultural University (Approval Number: SKLAB-2012-11). We have complied with all relevant ethical regulations for animal use. The 5 weeks old female ICR mice were procured from Beijing Vital River Laboratory Animal Technology.

The OG cell lines were maintained on feeder cells using a basic serum/LIF medium. This medium comprised DMEM (Gibco, 10829018), 15% FBS (Gibco, 10099), 1% penicillin/streptomycin (Gibco, 15104122), 1% non-essential amino acids (Gibco, 11140050), 1% GlutaMAX (Gibco, 35050079), 106 units/L of mouse LIF (Millipore, ESG1106) and 100mM -mercaptoethanol (Gibco, 15104122). The feeder cells were treated with mitomycin C (Amresco, MJ594) to inhibit their growth and were cultured in DMEM (Gibco, 11960) supplemented with 10% FBS (Gibco, 10099), 1% penicillin/streptomycin (Gibco, 15104122), 1% non-essential amino acids (Gibco, 11140050) and 1% sodium pyruvate (Gibco, 15104122). Other small molecules mentioned in our article were procured from Selleck and added individually to the basal serum/LIF medium at varying concentrations. Subculturing of all cell lines was performed every 23 days at a ratio ranging from 1:6 to 1:10 using Tryple (Gibco, 12605028). To establish the MERVL-tdTomato reporter cell lines, the OG cell lines underwent transfection via electroporation and were subsequently selected using 1g/ml puromycin for 7 days. Clones were then isolated and confirmed through polymerase chain reaction (PCR) analysis. All cell lines were maintained in a humidified incubator at 37C with 5% CO2.

The CRISPR-Cas9 DNA library contained 130,209 sgRNAs about 20,611 genes constructed by our laboratory. To obtain the mutant cell library, we transfected 108 OG cells with the MERVL reporter by electroporation (2B Nucleofector System, Lonza). After 24h transfection, the cells were selected with 350ng/l G418 (InvivoGen, ant-gn-5) for 7 days. We expanded these cells to 3108 for primary screen. We collected 2C-positive cells using FACS and amplified them for consecutive screen. Each round of screening was repeated three times. Medium needed to be changed every day.

Genomic DNA were extracted from 108 cells of the mutant cell pool and 510106 cells of 2C-postive from the consecutive screen. The integrated sgRNA sequences were amplified by PCR using Gotaq DNA Polymerase (Mei5bio, MF002) with the left primer (5-AATGATACGGCGACCACCGAGATCTACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNNNNNTGAAAGTATTTCGATTTCTTGG-3) and the right primer (5- CAAGCAGAAGACGGCATACGAGATNNNNNNNNGTGACTGGAGTTCAGACGTGTGCTCTTCCGATCTTGTTGATAACGGACTAGCCTTATT-3). Then PCR products were purified and sequenced by Illumina HiSeq TM4000. We used MAGeCK package to analyze our screening results and took Z-score into consideration. Ggplot2 was used to summarize these results.

To generate CRISPR KO cells, we designed two sgRNAs for each target gene and cloned them into the pSg6 Plasmid. Subsequently, we transfected 106 mESCs using the Lonza 2B Nucleofector System. Twenty-four hours after transfection, cells were subjected to selection with 350ng/l G418 for a duration of 7 days. Following selection, individual clones were isolated into a 48-well plate, and their targeted regions were verified. Detailed sequences of the sgRNAs can be found in TableS1.

Total RNA was extracted to amplify the CDS of Mdm2 by PCR. Subsequently, the amplified fragment was cloned into the PB vector under the control of the EF1 promoter. A total of 4g of the vector was transfected into 106 mESCs using the Lonza 2B Nucleofector System. Following transfection, mESCs were cultured for 24h and then subjected to selection with 350ng/l G418 for a period of 7 days. Clones were subsequently isolated and expanded in a 48-well plate to allow for the extraction of RNA and protein.

Total RNA was extracted from cells using the RaPure Total RNA Kits (Magene, R4011) following the manufacturers protocol. Subsequently, 1g of RNA was reverse transcribed into cDNA using the ABScript III RT Master Mix (Abclonal, RK20429). qPCR was conducted using the 2x RealStar Green Power Mix (Genestar, A311-10) on a Roche PCR machine. The relative quantification of each gene was achieved by normalizing to Gapdh. A complete list of primers utilized for qPCR can be found in TableS2.

Total RNA was purified using magnetic beads with Oligo (dT) to selectively isolate mRNA. RNA-seq libraries were subsequently constructed and assessed using a combination of TIANGEN Biotech and the Agilent 2100 BioAnalyzer. The sequencing process generated 150bp paired-end reads using PE150 on an Illumina platform. To analyze the data, clean reads were mapped to the Mus musculus genome using HISAT2. Read counts were quantified using HTSeq-count (v0.6.0) and then normalized to obtain the Fragments Per Kilobase of transcript sequence per Millions base pairs sequenced (FPKM) values. Differentially expressed genes (DEGs) were identified using edgeR with criteria including an absolute log2 (fold change)>2 and a p value<0.05. Subsequently, the datasets were further analyzed using the R programming language.

Cell sorting and analysis were carried out using the FACS CaliburTM flow cytometer (BD, San Jose, CA, USA). Data visualization was conducted using FlowJo software version 10. For our gating strategy, we employed wild-type (WT) mESCs with the MERVL reporter.

Collect 293T cells cultured in 10cm culture dishes using 1mL of IP lysis buffer (Beyotime, P0037), and transfer them to 1.5mL centrifuge tubes. Let them lyse on ice for 30min. After centrifugation at maximum speed (4C, 21,100g, 10min), collect the supernatant for subsequent Co-IP experiments. Supernatants were incubated with Pierce beads (Thermo Scientific, 88802) for 68h at 4C with rotation. Antibodies used include FLAG (Sigma, F1804, 1:200 mouse) and HA (Beyotime, AH158, 1:200 mouse), IgG (Beyotime, A7028, 1:200 mouse). The protein solution collected was denatured at 95C for 10min using 10% SDSPAGE for western blot analysis.

The cells were lysed using IP lysis buffer supplemented with 100 PMSF and incubated on ice for 30min. The supernatant was obtained by centrifuging at 4C and 20,000g for 15min. To determine protein concentration, we utilized the BCA protein assay kit (Beyotime, P0012) according to the manufacturers instructions. Equal amounts of protein were denatured using 10% SDSPAGE. For western blotting, the following primary antibodies were used: MDM2 (Abcam, ab259265, 1:1000 rabbit), SUZ12 (Cell Signal Technology, 3737, 1:1000 rabbit), ACTIN (Beyotime, AA128, 1:1000 mouse), TUBULIN (Beyotime, AF2835, 1:1000 mouse), HA (Beyotime, AH158, 1:1000 mouse), FLAG (Sigma, F1804, 1:1000 mouse), H3 (Elabscience, E-AB-22003, 1:1000 mouse) and H3K27me3 (Sigma, 07-449, 1:10,000 rabbit).

Embryos were subjected to fixation with 4% paraformaldehyde for a duration of 30min and subsequent permeabilization using 0.5% Triton X-100 for 30min at room temperature. Blocking of embryos was treated with 1% BSA in PBS supplemented with 0.1% Tween 20, lasting for 60min at room temperature. Incubation with CDX2 primary antibodies (Biogenex, MU392A, 1:200 mouse) occurred overnight at 4C, followed by incubation with secondary antibodies (Invitrogen, A32723, 1:500) for 1h at room temperature. Lastly, the nuclei of the embryos were stained with DAPI (Beyotime, P0131), and images were acquired using the fluorescence microscope.

Cells were fixed by incubating with 70% ethanol at 20C overnight. The next day, the fixed cells were centrifuged at 4C, 300g, and washed once with PBS. Afterward, RNase A treatment was performed at 37C for 30min. Finally, the cells were stained with propidium iodide (PI) at 4C for 30min. Cell cycle analysis was performed using a BD flow cytometer, and the data were analyzed with Modfit LT software to determine the distribution of cells across different phases of the cell cycle.

To inhibit the expression of Mdm2 in pre-ZGA embryos, zygotes were cultured in KSOM or HM medium supplemented with Nutlin-3 (Selleck, S1061) at a final concentration of 5M. DMSO was included as a negative control. The embryos were cultured at 37C and monitored daily until they reached the blastocyst stage.

CUT&Tag assay was conducted using the NovoNGS CUT&Tag 3.0 High-Sensitivity Kit (Novoprotein, N259). Approximately 1105 mESCs were incubated with 10L of Binding ConA beads. Primary antibodies targeting FLAG (Sigma, F1804, 1:50 mouse) and H3K27me3 (Sigma, 07-449, 1:100, rabbit) were incubated overnight at 4C. Subsequently, secondary antibodies were added, and the mixture was incubated at room temperature for 1h. Following this, the samples were treated with 1L of Transposome and incubated at room temperature for 1h. DNA was then collected for subsequent PCR analysis. The libraries were amplified and subjected to sequencing using the Illumina NovaSeq PE150 platform following the manufacturers instructions.

The raw data underwent quality filtering using Trimmomatic to obtain clean data. These clean data were then aligned to the mm10 genome using Bowtie2. For the identification of peaks, we utilized MACS2. Heatmaps were generated using Deeptools, and ChIPseeker was employed to annotate the promoters.

We conducted a re-analysis of publicly available datasets. H3K27me3 ChIP-seq data for mESCs and SUZ12 KO mESCs were obtained from GSE103685. Additionally, H3K27me3 modification data for 2C embryos were acquired from GSE73952, and RNA-seq data for mouse and pig pre-implantation embryos were retrieved from GSE71434 and GSE163709.

The statistical differences were analyzed by the Students t-test when two independent groups were compared. Data are displayed in a bar graph with error bars representing the meanSD and individual sample points shown. GraphPad Prism was used for the statistical analysis of data. *P<0.05, **P<0.01, ***P<0.001 and ****P<0.0001. Three independent biological replicates were included and the figure legends specify the sample sizes.

Detailed information on the research design can be found in the Nature Portfolio Reporting Summary associated with this article.

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Lai, A. C. & Crews, C. M. Induced protein degradation: an emerging drug discovery paradigm. Nat. Rev. Drug Discov. 16, 101114 (2017).

Article CAS PubMed Google Scholar

Nalawansha, D. A. & Crews, C. M. PROTACs: an emerging therapeutic modality in precision medicine. Cell Chem. Biol. 27, 9981014 (2020).

Article CAS PubMed PubMed Central Google Scholar

Kronke, J. et al. Lenalidomide causes selective degradation of IKZF1 and IKZF3 in multiple myeloma cells. Science 343, 301305 (2014).

Article PubMed Google Scholar

Lu, G. et al. The myeloma drug lenalidomide promotes the Cereblon-dependent destruction of Ikaros proteins. Science 343, 305309 (2014).

Article CAS PubMed Google Scholar

Kannt, A. & Dikic, I. Expanding the arsenal of E3 ubiquitin ligases for proximity-induced protein degradation. Cell Chem. Biol. 28, 10141031 (2021).

Article CAS PubMed Google Scholar

Belcher, B. P., Ward, C. C. & Nomura, D. K. Ligandability of E3 ligases for targeted protein degradation applications. Biochemistry 62, 588600 (2023).

Article CAS PubMed Google Scholar

Buckley, D. L. et al. Targeting the Von HippelLindau E3 ubiquitin ligase using small molecules to disrupt the VHL/HIF-1 interaction. J. Am. Chem. Soc. 134, 44654468 (2012).

Article CAS PubMed PubMed Central Google Scholar

Ito, T. et al. Identification of a primary target of thalidomide teratogenicity. Science 327, 13451350 (2010).

Article CAS PubMed Google Scholar

Spradlin, J. N. et al. Harnessing the anti-cancer natural product nimbolide for targeted protein degradation. Nat. Chem. Biol. 15, 747755 (2019).

Article CAS PubMed PubMed Central Google Scholar

Tao, Y. et al. Targeted protein degradation by electrophilic PROTACs that stereoselectively and site-specifically engage DCAF1. J. Am. Chem. Soc. 144, 1868818699 (2022).

Article CAS PubMed PubMed Central Google Scholar

Zhang, X. et al. DCAF11 supports targeted protein degradation by electrophilic proteolysis-targeting chimeras. J. Am. Chem. Soc. 143, 51415149 (2021).

Article CAS PubMed PubMed Central Google Scholar

Zhang, X., Crowley, V. M., Wucherpfennig, T. G., Dix, M. M. & Cravatt, B. F. Electrophilic PROTACs that degrade nuclear proteins by engaging DCAF16. Nat. Chem. Biol. 15, 737746 (2019).

Article CAS PubMed PubMed Central Google Scholar

Ghandi, M. et al. Next-generation characterization of the Cancer Cell Line Encyclopedia. Nature 569, 503508 (2019).

Article CAS PubMed PubMed Central Google Scholar

Nusinow, D. P. et al. Quantitative proteomics of the Cancer Cell Line Encyclopedia. Cell 180, 387402 (2020).

Article CAS PubMed PubMed Central Google Scholar

Khan, S. et al. A selective BCL-XL PROTAC degrader achieves safe and potent antitumor activity. Nat. Med. 25, 19381947 (2019).

Article CAS PubMed PubMed Central Google Scholar

Slabicki, M. et al. The CDK inhibitor CR8 acts as a molecular glue degrader that depletes cyclin K. Nature 585, 293297 (2020).

Article CAS PubMed PubMed Central Google Scholar

Slabicki, M. et al. Small-molecule-induced polymerization triggers degradation of BCL6. Nature 588, 164168 (2020).

Article CAS PubMed PubMed Central Google Scholar

Winter, G. E. et al. Phthalimide conjugation as a strategy for in vivo target protein degradation. Science 348, 13761381 (2015).

Article CAS PubMed PubMed Central Google Scholar

Nabet, B. et al. The dTAG system for immediate and target-specific protein degradation. Nat. Chem. Biol. 14, 431441 (2018).

Article CAS PubMed PubMed Central Google Scholar

Konermann, S. et al. Genome-scale transcriptional activation by an engineered CRISPRCas9 complex. Nature 517, 583588 (2015).

Article CAS PubMed Google Scholar

Tempest, P. A. Recent advances in heterocycle generation using the efficient Ugi multiple-component condensation reaction. Curr. Opin. Drug Discov. Devel. 8, 776788 (2005).

CAS PubMed Google Scholar

Soucy, T. A. et al. An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer. Nature 458, 732736 (2009).

Article CAS PubMed Google Scholar

Skaar, J. R., Pagan, J. K. & Pagano, M. SCF ubiquitin ligase-targeted therapies. Nat. Rev. Drug Discov. 13, 889903 (2014).

Article CAS PubMed PubMed Central Google Scholar

Cheng, J. et al. Emerging role of FBXO22 in carcinogenesis. Cell Death Discov. 6, 66 (2020).

Article CAS PubMed PubMed Central Google Scholar

Tan, M. K., Lim, H. J. & Harper, J. W. SCFFBXO22 regulates histone H3 lysine 9 and 36 methylation levels by targeting histone demethylase KDM4A for ubiquitin-mediated proteasomal degradation. Mol. Cell. Biol. 31, 36873699 (2011).

Article CAS PubMed PubMed Central Google Scholar

Johmura, Y. et al. Fbxo22-mediated KDM4B degradation determines selective estrogen receptor modulator activity in breast cancer. J. Clin. Invest. 128, 56035619 (2018).

Article PubMed PubMed Central Google Scholar

Johmura, Y. et al. SCFFbxo22-KDM4A targets methylated p53 for degradation and regulates senescence. Nat. Commun. 7, 10574 (2016).

Article CAS PubMed PubMed Central Google Scholar

Zhang, L. et al. FBXO22 promotes the development of hepatocellular carcinoma by regulating the ubiquitination and degradation of p21. J. Exp. Clin. Cancer Res. 38, 101 (2019).

Article PubMed PubMed Central Google Scholar

Ge, M. K. et al. FBXO22 degrades nuclear PTEN to promote tumorigenesis. Nat. Commun. 11, 1720 (2020).

Article CAS PubMed PubMed Central Google Scholar

Tian, X. et al. F-box protein FBXO22 mediates polyubiquitination and degradation of KLF4 to promote hepatocellular carcinoma progression. Oncotarget 6, 2276722775 (2015).

Article PubMed PubMed Central Google Scholar

Zhu, X. N. et al. FBXO22 mediates polyubiquitination and inactivation of LKB1 to promote lung cancer cell growth. Cell Death Discov. 10, 486 (2019).

Article Google Scholar

Liang, D. et al. Protein CutA undergoes an unusual transfer into the secretory pathway and affects the folding, oligomerization, and secretion of acetylcholinesterase. J. Biol. Chem. 284, 51955207 (2009).

Article CAS PubMed Google Scholar

Vinogradova, E. V. et al. An activity-guided map of electrophilecysteine interactions in primary human T cells. Cell 182, 10091026 (2020).

Article CAS PubMed PubMed Central Google Scholar

Backus, K. M. et al. Proteome-wide covalent ligand discovery in native biological systems. Nature 534, 570574 (2016).

Article CAS PubMed PubMed Central Google Scholar

Casement, R., Bond, A., Craigon, C. & Ciulli, A. Mechanistic and structural features of PROTAC ternary complexes. Methods Mol. Biol. 2365, 79113 (2021).

Article CAS PubMed Google Scholar

Hines, J., Lartigue, S., Dong, H., Qian, Y. & Crews, C. M. MDM2-recruiting PROTAC offers superior, synergistic antiproliferative activity via simultaneous degradation of BRD4 and stabilization of p53. Cancer Res. 79, 251262 (2019).

Article CAS PubMed Google Scholar

Galkin, A. V. et al. Identification of NVP-TAE684, a potent, selective, and efficacious inhibitor of NPM-ALK. Proc. Natl Acad. Sci. USA 104, 270275 (2007).

Article CAS PubMed Google Scholar

Koivunen, J. P. et al. EML4ALK fusion gene and efficacy of an ALK kinase inhibitor in lung cancer. Clin. Cancer Res. 14, 42754283 (2008).

Article CAS PubMed PubMed Central Google Scholar

Perez-Riverol, Y. et al. The PRIDE database resources in 2022: a hub for mass spectrometry-based proteomics evidences. Nucleic Acids Res. 50, D543D552 (2022).

Article CAS PubMed Google Scholar

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Dublin, July 05, 2024 (GLOBE NEWSWIRE) -- The "Plant Breeding and CRISPR Plant Market - Global Industry Size, Share, Trends, Opportunity, and Forecast, 2019-2029F" report has been added to ResearchAndMarkets.com's offering.

Global Plant Breeding and CRISPR Plant Market was valued at USD 11.16 billion in 2023 and is anticipated to project robust growth in the forecast period with a CAGR of 6.91% through 2029

Global agriculture landscape is undergoing a transformative phase with advancements in plant breeding and CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) technologies. These innovative approaches hold the promise of revolutionizing crop development, addressing the challenges of a growing population, climate change, and sustainable agriculture. In this article, we delve into the intricacies of the Global Plant Breeding and CRISPR Plant Market, examining key drivers, challenges, and the potential impact on global food security.

Global Plant Breeding and CRISPR Plant Market represent a frontier in agricultural innovation, offering solutions to pressing global challenges. As technology continues to evolve and stakeholders navigate regulatory landscapes, the potential for these advancements to drive sustainable agriculture and enhance global food security is substantial. The coming years are likely to witness further breakthroughs and collaborations that will shape the future of plant breeding and CRISPR technologies in the agricultural sector.

Precision Breeding

Precision breeding has emerged as a pivotal trend propelling the Plant Breeding and CRISPR Plant Market into a new era of innovation, particularly in the realm of disease resistance. The ability to edit genes using CRISPR technology precisely and specifically has revolutionized the development of crops with enhanced resistance to diseases, marking a paradigm shift in the agricultural landscape.

In the face of evolving and increasingly complex plant pathogens, precision breeding offers a targeted approach to fortify crops against specific diseases. Unlike conventional breeding methods, which may introduce unintended changes, CRISPR technology allows scientists to pinpoint and modify the genes responsible for conferring resistance. This precision not only accelerates the development timeline but also ensures the preservation of desirable traits in the modified crops.

The market's focus on precision breeding for disease resistance is driven by the imperative to address global food security challenges. Crop losses due to diseases can have severe economic and humanitarian impacts, making the development of resilient varieties a top priority. Biotechnology companies, researchers, and agricultural stakeholders are investing heavily in precision breeding techniques to create crops capable of withstanding the onslaught of pathogens, thereby ensuring stable yields and securing the global food supply.

Gene Editing Application

Gene editing applications, particularly the revolutionary CRISPR-Cas9 technology, are steering the Plant Breeding and CRISPR Plant Market towards unprecedented heights, with a laser focus on enhancing disease resistance in crops. This transformative approach to genetic modification has become a driving force, offering a level of precision and efficiency that traditional breeding methods struggle to match.

The ability to precisely edit specific genes responsible for disease resistance is a game-changer for agricultural sustainability. CRISPR-Cas9 enables researchers and biotech companies to tailor crops with enhanced immunity to specific pathogens, safeguarding against the economic and food security risks posed by plant diseases.

One of the key catalysts for the market's enthusiasm towards gene editing for disease resistance is the rapid development timeline. Traditional breeding methods often entail years of crossbreeding and selection processes, whereas CRISPR allows for targeted modifications in a fraction of the time. This accelerated pace is critical in responding to emerging and evolving plant pathogens.

The demand for disease-resistant crops is driven by the imperative to ensure stable and secure food production amidst a backdrop of changing climates and global uncertainties. As gene editing applications become increasingly refined and accessible, the market witnesses a surge in investments, collaborative research efforts, and commercialization strategies aimed at bringing disease-resistant varieties to farms worldwide.

Integration of Bioinformatics

The integration of bioinformatics into plant breeding and CRISPR technologies is ushering in a new era of precision and efficiency in the pursuit of disease-resistant crops. This strategic amalgamation of biological data analysis and genetic information has become a pivotal driver, shaping the landscape of the Plant Breeding and CRISPR Plant Market.

Bioinformatics enables researchers to analyze vast datasets with unprecedented speed and accuracy, expediting the identification of genes associated with disease resistance. This data-driven approach enhances the selection of target genes for modification, ensuring a more focused and effective genetic editing process.

The intricate relationship between bioinformatics and disease resistance is particularly crucial in addressing the constant threat of evolving pathogens. By deciphering the genetic basis of plant-pathogen interactions, scientists can design crops with tailored resistance mechanisms, bolstering the overall resilience of agricultural systems.

Moreover, the integration of bioinformatics streamlines the identification of potential off-target effects during CRISPR-mediated gene editing. This not only ensures the precision of genetic modifications but also addresses regulatory concerns and enhances the overall safety profile of genetically modified crops.

Regional Insights

The Asia-Pacific region stands at the forefront of driving the Plant Breeding and CRISPR Plant Market, fueled by its diverse agricultural landscape and the urgent need to address food security challenges. Countries like China and India are making substantial investments in research and development, leveraging CRISPR technology to enhance the traits of staple crops. Rice, a dietary staple for a significant portion of the global population, has been a focal point, with initiatives aimed at improving yield, nutritional content, and resilience to pests and diseases.

Furthermore, Asia-Pacific nations are actively collaborating with international biotech companies and research institutions. These collaborations not only facilitate the exchange of knowledge but also contribute to the development of region-specific crop varieties tailored to local agricultural needs.

In Europe, stringent regulatory frameworks have not deterred the pursuit of innovation in the Plant Breeding and CRISPR Plant Market. The region's commitment to sustainable agriculture aligns seamlessly with the goals of these technologies. Countries like the United Kingdom and Germany are investing heavily in research initiatives, focusing on developing crops with increased resistance to environmental stressors, reduced reliance on chemical inputs, and improved nutritional profiles.

The European Union's recent decision to regulate gene-edited crops based on the characteristics of the final product rather than the technology used provides a more nuanced regulatory approach. This shift has invigorated the industry, encouraging companies and researchers to explore the full potential of CRISPR technology in plant breeding.

North America, particularly the United States and Canada, is a key driver in the Plant Breeding and CRISPR Plant Market. The region's strong emphasis on technological innovation, coupled with a robust agricultural sector, has created an environment conducive to the adoption of these advanced breeding technologies.

Major biotechnology companies headquartered in North America are leading the charge in developing and commercializing genetically modified crops. The focus extends beyond staple crops to include cash crops like soybeans and corn, where CRISPR technology is employed to enhance traits such as drought resistance, pest tolerance, and improved yields.

Additionally, collaborations between North American research institutions and international partners contribute to the global pool of knowledge, further advancing the capabilities of Plant Breeding and CRISPR technologies.

Key Attributes:

Competitive Landscape

Company Profiles: Detailed analysis of the major companies present in the Global Plant Breeding and CRISPR Plant Market.

Report Scope:

Plant Breeding and CRISPR Plant Market, By Type:

Plant Breeding and CRISPR Plant Market, By Trait:

Plant Breeding and CRISPR Plant Market, By Application:

Plant Breeding and CRISPR Plant Market, By Region:

For more information about this report visit https://www.researchandmarkets.com/r/zbh2fy

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$16.7 Billion Plant Breeding and CRISPR Plant Market - Global Industry Size, Share, Trends, Opportunity, and Forecast ... - GlobeNewswire

Recommendation and review posted by Bethany Smith

Did you know the gut microbiome has over 100 trillion microbes consisting of bacteria, fungi, yeast, and viruses, all influencing how our body functions and responds to stress, certain foods, and even some medications? "There is so much attention and research on the microbiome and gut health now that experts often refer to it as the 'second brain,'" registered dietitian Kristian Kirkpatrick, RD, told Cleveland Clinic.

RELATED: Doctors Share 9 Signs You Have "Healthy Poop"And What to Do If You Don't.

According to Max Nieuwdorp, PhD, an endocrinologist and researcher, maintaining a healthy gut microbiome has many added benefits, such as a healthy hormone balance. In his most recent book, The Power of Hormones, Nieuwdorp explains that gut microbes play a pivotal role in the release and production of different hormones, which in turn affect many of our daily processes, like metabolism and mood. And this is why he recently shared three things you should avoid to keep your gut health in check. ae0fcc31ae342fd3a1346ebb1f342fcb

"The microbiome can really talk to the body by producing specific substances from the diet that are good or bad for you," Nieuwdorp told Business Insider. Those substances can have a positive or negative impact on the function of hormones. Because of this, Nieuwdorp is super particular about what he puts in his body.

One food group Nieuwdorp likes to avoid for optimal gut health is red meat. In his Business Insider interview, he explained that red meat alters the composition of the gut microbiome by producing "dangerous" metabolites during the digestion process.

"I try to not eat meat every day," he said.

While protein is good for you, building a meal plan that's centered around red meat can increase your risk for diabetes, heart disease, stroke, and colorectal cancer, per Scripps Health. Red meat is also high in cholesterol, saturated fats, and sodium.

RELATED: 9 Supplements That Can Damage Your Stomach, Doctors Say.

Nieuwdorp also avoids ultra-processed foodsfor example, sweetened breakfast cereals, processed meat, soda, and some frozen ready-to-eat meals. Instead, he prioritizes fresh foods that don't contain preservatives or additives.

"Ultra-processed foods contain large quantities of saturated fat and trans-fat, added sugar, salt, and food additives that seriously affect the gut and physical health," gastroenterologist Preeya Goyal, MD, explained in an interview with PIH Health. She added that consuming ultra-processed foods can also harmfully disrupt brain functions.

Finally, Nieuwdorp avoids taking antibiotics unless absolutely necessary. "They drive dysbiosis in the gut," he said.

Dysbiosis refers to a lack of diversity in microorganisms, explains Cleveland Clinic. This imbalance can make us "vulnerable to infections from germs living inside and outside of our bodies," their experts explain. "It can also interfere with other important services that our microbiomes normally provide for us."

With an imbalanced gut microbiome, our hormones can also be negatively affected.

We offer the most up-to-date information from top experts, new research, and health agencies, but our content is not meant to be a substitute for professional guidance. When it comes to the medication you're taking or any other health questions you have, always consult your healthcare provider directly.

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Hormone Doctor Shares 3 Things He Avoids for Gut Health Best Life - Best Life

Recommendation and review posted by Bethany Smith

Researchers believe that human bioidentical hormones confer a lower risk of breast cancer compared to conjugated estrogens.

Dear Dr. Roach: I am 62 years old and postmenopausal. I am reading more about bioidentical hormones giving added protection to the heart and brain, in addition to helping with hair loss and weight gain. However, it seems that the only way one can obtain these hormones is through nontraditional doctors. I havent asked my insurance yet if I can get these, but Im pretty certain that they will not prescribe these to me. (I will ask on my next visit.)

Can you offer any advice on the efficacy of these hormone replacement therapy (HRT) treatments? It seems past opinions about how HRT could lead to increased cases of breast cancer have changed.

P.M.

You are right that our understanding of the relationship between HRT and breast cancer, as well as heart disease, continues to evolve. HRT is approved to treat symptoms of menopause, such as hot flashes.

With increasing frequency, physicians prescribe bioidentical hormones rather than conjugated equine estrogens and medroxyprogesterone, which were tested in large trials. They showed an increased risk of coronary artery disease when given to women over 60 or women who are 10 years past menopause. They also showed an increased risk of breast cancer when they were used in combination.

Researchers believe that human bioidentical hormones confer a lower risk of breast cancer compared to conjugated estrogens. As long as they are given right after menopause, biodientical hormones have a low risk of heart disease. I do not start estrogen for women who are more than 10 years past menopause, due to the increased risk of heart attack. I also do not prescribe any oral estrogen in a woman with a history of breast cancer, and I consult with a womans oncologist before using any estrogen, even topical.

There are some doctors who use custom-compounded hormones, and the dosing may be based on blood levels. I dont advise custom compounding, as the safety and efficacy is not well-established; the potency is variable; and they are not subject to regulatory oversight. For this reason, when I prescribe HRT, I prescribe the FDA-approved bioidentical hormones that are extensively tested.

Although I frequently prescribe HRT for women with symptoms of menopause, I do not prescribe these regimens for the purpose of preventing heart or brain disease, as we know they have risks (including a small risk of blood clots). Also, the benefit in protection is unproven. Observational trials suggest that there may be a benefit in prevention of heart disease and breast cancer with the newer regimens, but I am await strong interventional studies before prescribing treatments to prevent disease.

My colleagues in gynecology tend to have more experience in prescribing HRT. After the release of the large trials, many internists stopped prescribing these medications, which is a shame because they remain highly effective for menopausal symptoms. When used properly, they are very safe for most women. However, I have had many readers tell me that they have been unable to find a physician who will prescribe these medicines for their symptoms, even if they are willing to take the risks.

Email questions to [emailprotected].

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Your Good Health: Some types of hormone replacement therapy are difficult to obtain - Times Colonist

Recommendation and review posted by Bethany Smith

Written by Stphane Viville

4 Jul, 2024

2 min read

Supported by ESHRE, a new project, the Female Reproductive Genetics Initiative (FeRGI), has been launched within the Special Interest Group (SIG) Reproductive Genetics.

This initiative is driven by recent progress in the field of infertility genetics and the need to translate this research into clinical practice. Over the past 15 years, significant advancements have been made in identifying non-syndromic infertility genes for both men and women. Now, it is imperative to translate this foundational research into clinical applications, particularly in diagnosis. To support this new endeavor, it is crucial to develop the necessary tools for training clinicians and biologists in reproductive medicine, genetic counseling, and creating a comprehensive database listing all genes and variants involved in female non-syndromic infertility phenotypes.

The team behind FeRGI comprises professionals in medically assisted reproduction (MAR), including basic and clinical scientists. They recently published a systematic review and evidence assessment of single-gene Gene-Disease relationships (GDRs) in human female infertility (Van Der Kelen et al., Hum Reprod Update. 2023). As this initiative is being developed within the Reproductive Genetics SIG, the steering committee also includes members within this SIG.

To make this new knowledge accessible, ESHRE and, more specifically, the Reproductive Genetics SIG, have agreed to host the FeRGI initiative. FeRGIs primary mission is to empower reproductive medicine practitioners in female infertility genetics by providing the resources and expertise they need to support better diagnoses and to enhance their professional capabilities in this new domain. To achieve this, we are establishing an interactive website enabling clinicians and biologists to access information on all genes associated with female infertility and their links to related phenotypes (GDRs). Additionally, the database will include an online form for researchers to submit newly identified gene variants.

Beyond data compilation, FeRGI serves as a hub for global collaboration and knowledge exchange. FeRGI will also organize educational activities, including regular scientific meetings, webinars, ESHRE campus workshops, and interactive internet programs, aiming to foster collaboration among experts in the field, young specialists, scientists, PhD students, and post-docs from around the world. By connecting genetic and reproductive specialists globally, we aim to stimulate research in genetics of female infertility and encourage its clinical implementation. Our website will offer an overview of our mission, planned activities, publications, and genetic data.

Guided by ethical considerations, FeRGI will be responsible for developing a best-practice guide/recommendation document. By shedding light on the genetic landscape of female infertility, FeRGI aims to ensure that advancements in technology are met with thoughtful reflection, while enhancing diagnosis, treatment, and fertility preservation for patients and their families.

Join Us in Shaping the Future

Together with ESHRE and the SIG Reproductive Genetics, FeRGI is shaping the future of female reproductive medicine. Join us on our journey as we illuminate the path towards fertility and family-building through genomic insights.

References

Van Der Kelen et al 2023. A systematic review and evidence assessment of monogenic gene-disease relationships in human female infertility and differences in sex development. Hum Reprod Update 29:218-232. doi: 10.1093/humupd/dmac044.

Verpoest W et al 2023. Genetics of infertility: a paradigm shift for medically assisted reproduction. Hum Reprod. 2023;38(12):2289-2295. doi: 10.1093/humrep/dead199.

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The Female Reproductive Genetics Initiative: let there be light. - ESHRE

Recommendation and review posted by Bethany Smith

Earthwork Portrait of Genghis Khan Christophe Boisvieux/Corbis

Since a 2003 study found evidence that Genghis Khans DNA was present in about 16 million men alive at the time, the Mongolian rulers genetic prowess has stood as an unparalleled accomplishment. But he isnt the only man whose reproductive activities still show a significant genetic impact centuries later. A 2015 study published in the European Journal of Human Genetics found that a handful of other men had prolific lineages, too.

To identify those lineages, the geneticists analyzed the Y chromosomes of more than 5,000 men from 127 populations spanning Asia, wrote Nature News Ewen Callaway in 2015. The Y chromosome is a part of the human genome handed down only from father to son. They found 11 Y-chromosome sequences that were each shared by more than 20 of the analyzed subjects. Chalk down one of those as Genghis Khans, and that leaves ten other men who initiated long-lived and widely spread family trees.

When he ruled during the 13th century, Genghis Khan presided over land that spanned from the Pacific coast of China to the Caspian Sea. Historians dont know exactly how many children Genghis Khan sired, but many agree his lineage is broad. In 1260, Persian historian Ata-Malik Juvaini wrote: Of the issue of the race and lineage of Chingiz [Genghis] Khan, there are now living in the comfort of wealth and affluence more than 20,000.

Mongol rulers such as Genghis Khan could have spread their genes widely, because of rapes during conquests and because the khans had access to many women in the areas they ruled, Oxford University geneticist Chris Tyler-Smith told Nicholas Wade of the New York Times in 2003.

Genghis Khans sons may have followed in their fathers footsteps and had large harems. Tushi, the emperors oldest son, had 40 sons himself, per the New York Times.

So, who were the other super-fertile fathers? One genetic sequence is attributed to Giocangga, the grandfather of the founder of the Qing dynasty. His Y chromosome was linked in a 2005 study to 1.5 million men in modern northern China. This large number likely resulted from his descendants taking many wives and concubines.

The other nine men are currently mysteries. Yet, by assuming they lived in the area where their genomes were most commonly found and by studying mutations in the genetic sequences, scientists suggest they originated throughout Asia between 2100 B.C.E. and 700 C.E., per Nature News.

According to Nature News, the founders who lived at the earlier end of this range, between 2100 B.C.E and 300 B.C.E., were part of both agricultural and nomadic cultures. They lived during the emergence of hierarchical, authoritarian societies in Asia. And the three lineages connected to more recent times, including those linked to Genghis Khan and Giocangga, were associated with nomadic peoples in Mongolia and northeast China.

Large genetic legacies are not confined to that part of the globe. According to a 2006 study in the American Journal of Human Genetics, 1 in 12 Irishmen worldwide can trace their heritage back to a single individual. That man may be a fifth-century Irish warlord dubbed Niall of the Nine Hostages, who could have as many as three million direct male descendants in modern times.

Genetic studies published in the last few years have continued to reveal more information about the heritage of peoples around the world. From uncovering the genetic history of the Viking age to confirming the origins of the Swahili people and pinpointing Neanderthal genes in modern populations, techniques analyzing ancient DNA have opened another window to understanding how genes flowed in the past.

As far as the nine unknown founders with impressive genetic lineages, more research is needed to discern their identities. But one thing is certain: Genghis Khan has never been the only big kid on the genetic block.

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Move Over, Genghis Khan. Many Other Men Left Huge Genetic Legacies - Smithsonian Magazine

Recommendation and review posted by Bethany Smith

"Gene therapy is the ultimate team sport within science, it's one of the reasons I love it, not only in terms of the stages of development of the product, but also often developing the gene or cell therapy itself. You need to figure out how you're going to deliver it, what's the route of administration? What's the capsid, or delivery vehicle that you're going to use? How do you design the transgene? How do you consider an animal model? That naturally lends itself to bringing together a lot of different expertise.

As gene and cell therapies grow in prevalence, continuing early research in the field is paramount to improving multiple aspects of these novel therapies. A number of researchers from Mass General Brigham (MGB) presented work dealing with new technologies and new methods aiming to improve gene and cell therapy and its delivery to different tissues, particularly the brain, atthe American Society of Gene & Cell Therapy (ASGCT) 27th Annual Meeting, held May 7 to 10, 2024, in Baltimore, Maryland.

CGTLivespoke with Nathan Yozwiak, PhD, head of research, Cell and Gene Therapy Institute, MGB, to learn more about the research presented at the meeting and other research that MGB is engaged in with cell and gene therapy. He discussed the MGB Gene and Cell Therapy Institute and emphasized its value as a resource for sponsors, investigators, and researchers involved with gene and cell therapies to hopefully speed up the process of developing these therapies. He stressed the importance of collaboration when developing and then assessing gene and cell therapies and how administrating these therapies is a big collaborative lift.

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Nathan Yozwiak, PhD, on Collaboration for Cell and Gene Therapy Development - CGTLive

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Berlin, Germany, June 21, 2024 Today Bayer AG, together with Charit Universittsmedizin Berlin, presented plans for the construction of the Berlin Center for Gene and Cell Therapies. The project is being substantially financed and supported by Germanys Federal Government as well as the State of Berlin. The aim of the joint project is to bring these groundbreaking technologies to patients more quickly while creating a leading biotech ecosystem for innovative therapies in Berlin.

The potential for cell and gene therapies (CGTs) is considered to be enormous. By targeting diseases at the genetic and cellular level, CGTs could offer options to people for whom conventional therapies have failed or where no effective treatment is currently available.

In order to translate basic research into benefits for patients faster, Charit and Bayer will establish the Berlin Center for Gene and Cell Therapies on the Bayer campus at Berlin Nordhafen. The center will support start-ups bringing their innovative approaches in the area of cell therapies and gene therapies into clinical development. To achieve this, the center will include a so-called incubator with fully equipped laboratory space and a production area certified according to the standards of good manufacturing practice (GMP). Incubators are facilities that accompany start-ups developing their innovative ideas and helping them build viable business models. These early-stage companies will receive advice on regulatory requirements, clinical trials, patent rights and business development. To operate the incubator, Bayer and Charit will establish a joint public-private, non-profit company with limited liability. Charit will own 67 percent of this company, with Bayer owning the remaining 33 percent.

The Berlin Center for Gene and Cell Therapies will bring together research, development and the manufacturing of cell therapies and gene therapies in the heart of Berlin. Purposely embedding it within the Berlin ecosystem, a European capital with a large number of biomedical and healthcare facilities, it is intended to become a creative and interactive hub for biotech innovations in the area of CGT. The project is funded by both the Federal Ministry of Education and Research and the State of Berlin. Construction is planned to begin in 2025.

Olaf Scholz, Federal Chancellor of Germany: "With the kick-off of the new translation center, we are also celebrating a unique form of collaboration between science, industry and politics. This institution will become the core of an entire organism of gene and cell-based therapies. To achieve this, we need scientists and entrepreneurs who see both the smallest details in the cell nucleus as well as the big picture: the medicine of the future that provides answers to the big questions that Rudolf Virchow already posed. Here in Germany we have both: bold research and innovative companies. I wish you every success with this visionary project!"

Bettina Stark-Watzinger, Federal Minister of Education and Research: Gene and cell therapies offer a tremendous opportunity for more targeted and therefore better treatment of patients. Currently, however, the path from the research laboratory to the patient's bedside often still takes too long. With the translation center for gene and cell therapies, we are now taking a big step forward in Germany. Science and industry are coming together in one location to turn ideas into reality and to help translate scientific findings into medical practice more quickly through spin-offs and start-ups. As an essential component of the National Strategy for Gene and Cell Therapies, the Federal Ministry of Education and Research is supporting the establishment of the Center with around

80 million euro. In doing so, we are once again strengthening Germany's position as a leading location for biomedical innovations.

Prof. Dr. Karl Lauterbach, Federal Minister of Health: Targeted gene therapies, personalized cancer vaccines and novel antibody-drug conjugates, together with artificial intelligence, will open a new era in medicine and entirely new prospects for patients. These revolutionary treatment approaches place high demands on laboratories, hospitals and doctors. This joint project of Bayer and Charit is an ideal partnership to learn together and make rapid progress.

Bill Anderson, Chairman of the Board of Management (CEO) of Bayer AG: Despite great advances in research and technology, there are still many diseases that are without cure and which affect the lives of millions. To these people, cell and gene therapies offer great hope. Only through close partnerships across borders, new approaches and quick action can we make real progress towards our objective of curing diseases that were long considered incurable.

Stefan Oelrich, Member of the Board of Management, Bayer AG and President of Bayers Pharmaceuticals Division: The close proximity between research and production within the Berlin Center for Gene and Cell Therapies will be unique in Germany. Together with the Charit we want to help translate scientific knowledge in the area of cell therapies and gene therapies into innovative treatment approaches for patients as quickly as possible. With the Berlin Center for Gene and Cell Therapies, it is our vision to establish a biotech ecosystem, which unites different players, providing international appeal way beyond the city of Berlin.

Prof. Dr. Heyo K. Kroemer, Chief Executive Officer of Charit: Cell therapies and gene therapies represent a major medical advance; they can help where conventional methods reach their limits. As these are highly innovative drugs, their development, however, is much more complex than that of other medicines. If we want to bring these therapies to patients as quickly as possible, we need to take new routes. With the intensified partnership between Charit and Bayer, we want to initiate structural development to bring Berlin to the forefront of this pioneering technology both nationally and internationally. In doing so, we also create and maintain value and thus jobs in the country. This is a big step in Berlin, for Berlin and for Germany.

Astrid Lurati, Chief Financial and Infrastructure Officer of Charit: "As part of this project, the two partners Charit and Bayer are combining their respective expertise to further advance the developments in the field of gene and cell therapy both nationally and internationally. This approach is unique in Germany and demonstrates the innovation power of Berlin and its major healthcare players in their efforts to reimagine the medical care of tomorrow already today. The extensive support, which we are receiving both from the State of Berlin as well as the Federal Government underlines the importance of this project. With the Berlin Center for Gene and Cell Therapies we are breaking new ground together and I would like to thank everyone involved for the excellent cooperation."

Kai Wegner, Governing Mayor of Berlin: Berlin is a strong and leading location for science, research and medicine and therefore for the healthcare industry as a whole. The newly emerging translation center for gene and cell therapies is an excellent example of this. The State of Berlin has supported this lighthouse project from the beginning as we are convinced of the potential that gene and cell therapies provide. The collaboration between Charit and Bayer in one of the most innovative areas of medicine is a clear signal that together we can make Berlin and Germany a pioneer in this field. It is our common goal to help more patients with the most modern therapies, where todays medicine still reaches its limits. In addition, the location provides an excellent environment, which we will continue to strengthen by further developing the Bayer site into a life science campus.

Franziska Giffey, Mayor and Berlin State Senator for Economic Affairs, Energy and Public Enterprises: The close collaboration between companies and the excellent research in the city is a recipe for success to achieve our goal of making Berlin the number one innovation hotspot in Europe. With the Bayer and Charit translation center for gene and cell therapies we are moving a big step closer to reaching this goal. It brings together two internationally renowned medical pioneers and will benefit from its location in Berlin, one of the most successful start-up ecosystems in the world. The new center has enormous economic potential and will attract talent and investment. This is very good news for the growing business location of Berlin.

The Berlin Center for Gene and Cell Therapies is being developed by iQ spaces, a project developer specialized in laboratory real estate, on the Bayer campus at Berlin Nordhafen. Across 18,000 sqm, the ten-story building is divided into an incubator with fully equipped laboratory and office space to accommodate 15 to 20 start-ups in various stages of development, as well as a GMP-certified manufacturing facility for the development of cell and gene therapies up to clinical phase II. The building was designed by the architectural firm HENN.

About cell therapies and gene therapies Cell therapies and gene therapies (Advanced Therapy Medicinal Products, ATMPs) are among the most important innovations in the healthcare sector. They have the potential to fundamentally change the treatment of cancer, autoimmune diseases, neurodegenerative diseases and many rare genetic diseases. The novel therapies are based on genes, tissues or cells and therefore often contain living components. These products, which are therefore also referred to as living drugs, can be better tailored to individual patients than traditional medicines and are particularly suitable for the treatment of diseases that were previously untreatable or difficult to treat. Although several hundred clinical studies for the development of cell therapies and gene therapies are currently ongoing, only a small number of such products is currently approved in Europe. The goal of Bayer and Charit is for the Berlin Center for Gene and Cell Therapies to bridge this translation gap.

About Charit Universittsmedizin Berlin With more than 100 departments and institutes across four campuses and 3,293 beds, Charit Universittsmedizin Berlin is one of Europes largest university medical centers. At Charit, the areas of research, teaching, and medical and patient care are closely interconnected. Averaging about 20,000 employees Charit-wide and some 23,500 across the entire group of companies, Berlins university medicine organization remained one of the capital citys largest employers in 2023. Charit is a leader in diagnosis and treatment of particularly severe, complex, and rare diseases and health conditions. A medical school and university medical center in one, Charit enjoys an outstanding reputation worldwide, combining first-class patient care with excellence in research and innovation, state-of-the-art teaching, and high-quality training and education. Everything Charit does revolves around people and their health. Charit pursues translational research in which scientific findings are applied to prevention, diagnostics, and treatment and clinical observations inform new approaches in research in turn. At Charit, the goal is to actively help shape the medicine of the future to benefit patients. https://www.charite.de/en/

About Bayer Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. In line with its mission, Health for all, Hunger for none, the companys products and services are designed to help people and the planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to driving sustainable development and generating a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2023, the Group employed around 100,000 people and had sales of 47.6 billion euros. R&D expenses before special items amounted to 5.8 billion euros. For more information, go to http://www.bayer.com.

Find more information at https://pharma.bayer.com/ Follow us on Facebook: http://www.facebook.com/bayer

Forward-Looking Statements This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayers public reports which are available on the Bayer website at http://www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

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Berlin Center for Gene and Cell Therapies kicked off in Berlin - The Palm Bayer

Recommendation and review posted by Bethany Smith

For a third time, Sarepta Therapeutics has convinced a top Food and Drug Administration official to overrule the prevailing view of their staff and approve a drug for Duchenne muscular dystrophy.

On Thursday evening, the FDA announced it expanded the approval of Elevidys, Sareptas Duchenne gene therapy, to cover nearly all patients, regardless of age or wheelchair status, despite the fact that the drug failed a large, Phase 3 trial last year.

That decision, documents concurrently released by the agency show, was made almost exclusively by Peter Marks, the agencys director of the Center for Biologics Evaluation and Research. He overruled three review teams and two top lieutenants, who wrote that the data Sarepta submitted cast significant uncertainty regarding the benefits of treatment.

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Top FDA official Peter Marks overruled staff to approve Sarepta gene therapy - STAT

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Visiongain has published a new report entitled Cell & Gene Therapy Cold Chain Logistics Market Report 2024-2034: Forecasts by Component (Cryogenic Shippers, Cryogenic Storage Freezers, Ultra-Low Freezers, Cold Chain Management Systems, Shipment and Storage Medium, Cryogenic Packout Kits, Others), by Services (Transportation, Storage, Packaging), by Mode of Transport (Air Transport, Ground Transport, Water Transport), by Holding Temperature Range (Cryogenic, Refrigerated, Ambient, Others), by End-users (Biopharmaceutical and Biotechnology Companies, Academic & Research Institutes, Others) AND Regional and Leading National Market Analysis PLUS Analysis of Leading Companies.

The global cell and gene therapy cold chain logistics market is estimated at US$1,877.3 million in 2024 and is projected to grow at a CAGR of 15.5% during the forecast period 2024-2034.

Escalating Adoption of Cell Therapies and Gene Therapies is Driving the Demand for Cold Chain Logistics

Recent advancements in cell and gene therapy have led to the approval of numerous novel treatments for conditions such as blood disorders and cancer. On March 14, 2024, the FDA granted approval to Bristol Myers Squibb's Breyanzi, marking it as the inaugural CAR T cell therapy for the treatment of relapsed or refractory chronic lymphocytic leukaemia (CLL) and small lymphocytic leukaemia. Additionally, on February 17, 2024, the FDA granted accelerated approval to Iovance Biotherapeutics' Amtagvi, a one-time cell therapy for unresectable or metastatic melanoma, with ongoing studies to confirm its efficacy. As the adoption of these therapies increases, the demand for proper storage, distribution, and logistics of cell and gene therapy products is expected to rise. Transporting these therapies to various countries requires a highly controlled and regulated process to ensure their safety and efficacy, which will significantly boost the cold chain logistics market.

Download Exclusive Sample of Report https://www.visiongain.com/report/cell-gene-therapy-market-2024/#download_sampe_div

How will this Report Benefit you?

Visiongains 359-page report provides 146 tables and 198 charts/graphs. Our new study is suitable for anyone requiring commercial, in-depth analyses for the cell and gene therapy cold chain logistics market, along with detailed segment analysis in the market. Our new study will help you evaluate the overall global and regional market for Cell and Gene Therapy Cold Chain Logistics. Get financial analysis of the overall market and different segments including type, process, upstream, downstream, and company size and capture higher market share. We believe that there are strong opportunities in this fast-growing cell and gene therapy cold chain logistics market. See how to use the existing and upcoming opportunities in this market to gain revenue benefits in the near future. Moreover, the report will help you to improve your strategic decision-making, allowing you to frame growth strategies, reinforce the analysis of other market players, and maximise the productivity of the company.

What are the Current Market Drivers?

Growth in Cancer and Genetic Disorders

Genetic disorders, stemming from abnormalities in genetic makeup and chromosomes, present a range of physical and mental health challenges globally. Disorders like alpha-1 antitrypsin deficiency, cystic fibrosis, beta thalassemia, haemophilia, and sickle cell disease have gained prominence due to factors including heightened awareness, advancements in diagnostic technology, and environmental and lifestyle changes. Low-income nations, in particular, face challenges such as inadequate diets, exposure to environmental toxins, and unhealthy lifestyles, increasing the risk of genetic abnormalities.

The WHO estimates that 5% of the global population carries sickle-cell disease, hemoglobin disorders, or thalassaemia, with over 300,000 babies born annually with severe hemoglobin disorders. Thalassemia, prevalent in regions like the Mediterranean, Middle East, Southeast Asia, and Africa, affects approximately 4.4 out of every 10,000 live births globally, with up to 40% of Southeast Asia's population being genetic carriers. These factors are poised to drive demand for cell and gene therapies in these regions, further emphasizing the necessity for proper transportation and storage of these biotherapeutics.

Increasing Strategic Initiatives Among Market Players Are Shaping the Industry's Future

The intricate processes involved in manufacturing, storing, and delivering cell and gene therapies demand a high level of expertise, specialized infrastructure, and adherence to stringent regulatory standards for global distribution. Major market players, spanning manufacturers to specialized logistics companies, are increasingly pursuing strategic initiatives such as launching new services and products, forging collaborations, and forming agreements to ensure the safe and efficient storage and transportation of these temperature-sensitive biologics. Regulatory bodies are also actively involved, offering crucial support to ensure compliance with international regulations and guidelines for therapeutic transportation. Significant initiatives include AmerisourceBergen's World Courier announcing the implementation of a real-time location monitoring solution across its multi-use packages in April 2023, aimed at enhancing shipment visibility during transit on a global scale.

Get Detailed ToC https://www.visiongain.com/report/cell-gene-therapy-market-2024/

Where are the Market Opportunities?

Stringent Government Regulations for Cell and Gene Therapy Transportation Are Expected to Boost the Market Growth

Stringent government regulations for cell and gene therapy transportation and storage present significant growth opportunities for market players by necessitating strict compliance measures. Companies must adhere to meticulous documentation standards, such as detailed records of temperature monitoring and handling procedures. For example, logistics providers like DHL and UPS offer specialized software to streamline these processes, ensuring regulatory compliance. Validation of cold chain processes is critical, involving extensive studies and costs to confirm the efficacy of temperature-controlled packaging, as seen with services from companies like Pelican BioThermal. Quality control measures, including audits and real-time monitoring, are essential for maintaining product integrity, with firms like Cryoport exemplifying strict adherence to these standards, thereby ensuring the safe and effective delivery of biologic products.

Surge in Cell and Gene Therapies Pipeline

The cell and gene therapy landscape is witnessing a surge in clinical pipeline strength and product approvals, propelled by technological advancements and substantial investments in research and development. This momentum is driving a significant increase in clinical studies focused on cell and gene therapeutics across various medical indications, extending beyond genetic disorders. Major biopharmaceutical companies are actively exploring the potential of these therapies for a diverse range of conditions.

Recent clinical findings have highlighted promising outcomes, particularly in areas like autoimmune disorders, where therapies such as regulatory T cells and mesenchymal stem cells have shown potential as future drug candidates, with approximately 1000 cell and gene therapies currently in the product development pipeline. For instance, on 4 January 2024, AbbVie and Umoja Biopharma announced two exclusive agreements to develop CAR-T cell therapies using Umoja's VivoVec platform. In future approval of these temperature sensitive biotherapeutics is estimated to increase necessity for temperature controlled and specific storage and transportation of these biologics to patients and healthcare providers in various parts of the globe.

Competitive Landscape

The market is highly fragmented with a lot of companies and products available for cold chain logistics of cell and gene therapies. The major players in the market are Cencora, Inc., Cardinal Health, Catalent Inc., Thermo Fisher Scientific Inc., Marken (a UPS Company), A.P. Moller Maersk, CryoPort Inc., DHL, FedEx, Arvato SE, NMDP BioTherapies, BioLife Solutions Inc., BioStor Systems Inc., Yourway, Atelerix Ltd., Nordic Cold Chain Solutions, MasterControl Solutions, Inc., TrakCel, Modality Solutions, and sedApta s.r.l. Companies focusing on the cell and gene therapy cold chain market utilize specialized solutions, integrated logistics, and regulatory compliance expertise. Modality Solutions and CryoPort Inc. offer customized cold chain processes, whereas DHL, FedEx, and Marken provide temperature-controlled global logistics services. Cardinal Health and Modality Solutions excel in regulatory compliance, assisting clients in navigating industry regulations to ensure the safe transportation of therapies.

Recent Developments

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Cell and Gene Therapy Cold Chain Logistics market is projected to grow at a CAGR of 15.5% by 2034: Visiongain - GlobeNewswire

Recommendation and review posted by Bethany Smith

The CIFFREO trial (NCT04281485) of fordadistrogene movaparvovec, an investigational mini-dystrophin gene therapy for Duchenne muscular dystrophy (DMD) developed by Pfizer, did not meet its primary end point of motor function improvement vs placebo among boys aged 4 to 7 years, the company announced in a press release.1

Improvement in motor function among ambulatory patients, determined by change in North Star Ambulatory Assessment at 1 year post treatment, was the main end point in the study. There were also no significant improvements in key secondary end points, including 10-meter run or walk speed and time to rise from floor.

While the question of gene therapys long-term efficacy remains, it is a promising route of therapy for patients with DMD | Image credit: luchschenF - stock.adobe.com

We are extremely disappointed that these results did not demonstrate the relative improvement in motor function that we had hoped, Dan Levy, MD, PhD, development head for Duchenne muscular dystrophy at Pfizer, said in a statement. We plan to share more detailed results from the study at upcoming medical and patient advocacy meetings, with the goal of ensuring that learnings from this trial can help improve future clinical research and development of treatment options that can improve care for boys living with Duchenne muscular dystrophy. We are grateful for the boys, their families, advocates, and the investigators who have participated in this research and the continuing effort to advance treatment options for this debilitating disease.

While the overall safety profile of the treatment was largely manageable in the CIFFREO trial, the study has paused dosing in its crossover portion due to a fatal serious adverse event in the phase 2 DAYLIGHT trial (NCT05429372), a multicenter, single-arm study evaluating safety and dystrophin expression after treatment with fordadistrogene movaparvovec in boys aged 2 to less than 4 years.2 In a community letter, Pfizer announced the loss of the patient but was still working to understand the its cause at the time.3

In the CIFFREO trial, adverse events were generally mild to moderate, and serious treatment-related adverse events generally responded to clinical management.1

DMD, the most common form of muscular dystrophy in children, is characterized by muscle breakdown over time due to patients without a functional dystrophin gene.4 Patients with DMD produce little to no dystrophin, which is a crucial protein for muscle strength.

Gene therapy is a promising area of research for patients with DMD, with the goal being to stabilize the disease by inducing production of a shortened but functional version of dystrophin. Lost muscle cannot be brought back by gene therapy, so it is not a curative therapy, but gene therapies have demonstrated promise for symptom mitigation and even strength improvement among some children.

The first gene therapy for DMD was FDA approved in June 2023 for patients aged 4 through 5 years.5 Delandistrogene moxeparvovec-rokl (Elevidys) was approved through the FDAs accelerated approval pathway and remains the only approved gene therapy for this patient population. The treatment was given the green light based on data from a randomized trial establishing increased expression of micro-dystrophin protein in treated patients.

While the question of gene therapys long-term efficacy remains, it is a promising route of therapy for patients with DMD.4 Alternative approaches to delivery are also being studied, with an aim of better targeting the muscles that need dystrophin or producing versions of dystrophin that are more functional compared with current gene therapies.

References

1. Pfizer provides update on phase 3 study of investigational gene therapy for ambulatory boys with Duchenne muscular dystrophy. News release. Pfizer. June 12, 2024. Accessed June 19, 2024. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-provides-update-phase-3-study-investigational-gene

2. Study of fordadistrogene movaparvovec in early stage Duchenne muscular dystrophy. ClinicalTrials.gov. Updated April 4, 2024. Accessed June 19, 2024. https://www.clinicaltrials.gov/study/NCT05429372

3. Update on Pfizers phase 2 gene therapy trial for Duchenne. Parent Project Muscular Dystrophy. May 7, 2024. Accessed June 19, 2024. https://www.parentprojectmd.org/update-on-pfizers-phase-2-gene-therapy-trial-for-duchenne/

4. Gene therapy for Duchenne muscular dystrophy. Childrens Hospital of Philadelphia. Accessed June 19, 2024. https://www.chop.edu/gene-therapy-duchenne-muscular-dystrophy

5. FDA approves first gene therapy for treatment of certain patients with Duchenne muscular dystrophy. News release. FDA. June 22, 2023. Accessed June 19, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-treatment-certain-patients-duchenne-muscular-dystrophy

Continue reading here:
Phase 3 CIFFREO Trial of DMD Gene Therapy Misses Primary End Point - AJMC.com Managed Markets Network

Recommendation and review posted by Bethany Smith

This is a developing story and will be updated with new information as it becomes available.

The FDA has approved Sarepta Therapeutics delandistrogene moxeparvovec-rokl (marketed as Elevidys), an adeno-associated virus (AAV) vector-based gene therapy for patients with Duchenne muscular dystrophy (DMD), for an expanded indication in the disease.1 The therapy is now approved for ambulatory patients (via traditional approval) and nonambulatory patients (via accelerated approval) with a confirmed mutation in the DMD gene who are 4 years of age or older and who do not have any deletion in exon 8 or exon 9 in the gene.

Representing many years of dedicated research, development, investment and creative energy, the expansion of the Elevidys label to treat Duchenne patients aged 4 and above, regardless of ambulatory status, is a defining moment for the Duchenne community," "Today also stands as a watershed occasion for the promise of gene therapy and a win for science, Doug Ingram, JD, the president and chief executive officer of Sarepta, said in a statement.1 At this pivotal moment, I want to give warm thanks to Drs. Jerry Mendell and Louise Rodino-Klapac for their dogged, 20-year pursuit of a gene therapy to treat this ruthless and life-robbing disease, to the FDA for following the scientific evidence to speed delivery of a therapy for a life-threatening rare disease to waiting patients, and to the many clinical investigators and courageous Duchenne families who have participated in the multiple studies that led to this important day.

Elevidys was originally granted FDA approval under an accelerated approval pathway for a more limited indication on June 22, 2023.2 That original decision limited the therapy's use to ambulatory patients aged 4 through 5 years withDMD and a confirmed mutation in theDMDgene, excluding patients with any deletion in exon 8 and/or exon 9. Today's decision, which was based on the agency's confirmation of functional benefits, additionally converts the accelerated approval to a traditional approval for patients who are ambulatory. Although it also expands eligibility to nonambulatory patients, the therapy remains under an accelerated approval for patients who are nonambulatory.1 Sarepta noted that ongoing approval for patients who are nonambulatory may depend on the results of ENVISION (Study SRP-9001-303), a phase 3 confirmatory clinical trial evaluating the gene therapy in patients with DMD who are nonambulatory or older and ambulatory.

Todays expansion of the Elevidys label represents the culmination of my 50-year pursuit of a treatment for Duchenne patients and, along with my colleague Dr. Louise Rodino-Klapac, a nearly 20-year effort to optimize and develop a gene therapy that could be safely and effectively delivered to muscle, Jerry Mendell, MD, the coinventor of Elevidys and the senior advisor for Medical Affairs at Sarepta added to the statement.1 The initial approval of Elevidys was a significant milestone, and the expanded indication means clinicians now have a treatment option for the great majority of boys and young men living with Duchenne. This expansion speaks to the success of the science, the evidence, and the improvements in the trajectory of the disease we have seen to date across studies.

Elevidy's original approval in 2023 was based upon data from the phase 1/2 SRP-9001-101 (NCT03375164) study, the phase 2 SRP-9001-102 study, and the phase 1 ENDEAVOR study (SRP-9001-103; NCT04626674).2 Changes in expression of microdystrophin, a surrogate end point, informed the approval. Furthermore, in the 20-patient cohort 1 of ENDEAVOR, announced in July 2022, findings showed that SRP-9001-treated patients improved 4 points from their pre-therapy baselines on the North Star Ambulatory Assessment (NSAA) compared with a propensity-weighted external control group (P < .0001) over 1 year.3 These patients demonstrated a 3.8-point (unadjusted means) and 3.2-point (least squared means) improvement that diverged from the natural history of DMD over time.

More recently, results from EMBARK, another phase 3 clinical trial (NCT05096221) evaluating Elevidys in DMD, were presented atthe American Society of Gene & Cell Therapy (ASGCT) 27th Annual Meeting, held May 7 to 10, 2024, in Baltimore, Maryland, by Damon Asher, MS, PhD, senior director of global medical affairs at Sarepta Therapeutics.4 Notably, EMBARK failed its primary end point. However, key secondary endpoints of change in time to rise (TTR) and time to walk/run 10 meters (10MWR) had small but significant differences from placebo, with a least square mean (LSM) difference of -.64 seconds (standard error [SE], 0.21; P = .0025) on TTR and an LSM of -0.42 seconds (SE, 0.15; P = .0048) on 10MWR.5 A composite, prespecified global statistical test including NSAA, TTR, 10MWR, Stride Velocity 95th Centile, 100MWR, and ascend 4 steps test was statistically significant compared with placebo (P = .0044).4

What's really going to tell the story is as these patients are followed over longer periods of time," Asher told CGTLive during the conference. "Theres a lot of challenges in showing efficacy, even with something that may be fairly efficacious, over such a short period of time."

Read more from the original source:
FDA Approves Sarepta's DMD Gene Therapy Elevidys for Expanded Indication - CGTLive

Recommendation and review posted by Bethany Smith