In 2018, more than forty-seven thousand Americans died from an opioid overdose, and ten million misused prescription opioids. The highly addictive drugs have destroyed lives and families, regardless of income level, race, age, or gender.

Fair Vassoler, a neuroscientist at Cummings School of Veterinary Medicine has spent years researching opioid use in rats and the effects the drugs have on the rats offspring. We recently sat down with her to discuss what her research can tell us about opioid addiction in humans.

Tufts Now: The United States is in the midst of an opioid addiction crisis. Why study opioid addiction in rats? Whats the advantage of studying that species?

Fair Vassoler: Rats have the same reward system as humans. In the wild, these systems are designed to get an individual to repeat a behavior because they find it pleasurable, like eating and mating. Its really for survival of the species. Because rats and humans have the same reward system, rats can be great models for human addiction and human substance-use disorder. We have a huge amount of literature already about rats and their responses to drugs of abuse, and their behaviors are very similar to what we see in humans.

We can see escalating behaviors in the rats where they take more and more drugs if you give them more access. We see the same thing in humans. We can see relapse behaviors in rats the same way that we see them in humansif you take the drug away and then put the rats back in an environment that reminds them of the drug, theyll start searching for it just the way a human would.

With rats, we can look at what is happening in the brain at that time. We can record data from different parts of the brain and see what changes are happening and relate those changes back to humans.

Your research looked at how opioid addiction affected the rats offspring. What did you find?

When the parents were adolescents, they were given injections of opioids for ten days, and then we stopped giving them any more opioids. So it was very brief exposure. We let them grow up to adulthood, then mated them and looked at their offspring to determine if the offspring were more or less likely to take opioids or cocaine.

We found that if the rats fathers had been exposed to opioids, then the rats were more likely to take opioids and worked harder to obtain opioids. But they were less likely to take cocaine.

If the rats mothers had taken opioids, we found exactly the opposite. The rats had decreased likelihood to take opioids and increased likelihood to take cocaine.

We looked at both drugs because a lot of people think substance-use disorder is substance-use disorder. You may think that if someone is interested in taking drugs, then theyd be interested in taking all the drugs. But the rats definitely discriminated, and this can give us clues about which part of the brain is changed.

What is the practical application for this research right now? Can any of it translate to humans?

Its not that we can take the results and say that humans would be the same as rats. Humans are a very tricky species to study because they have so many different environmental experiences that are hard to control for. But I do think our research can suggest which areas are vulnerable, such as how a predisposition to addiction can get passed on from one generation to the next, and different places for intervention.

We have to think about how this widespread exposure to opioids is going to be impacting the next human generation. If we can find the right interventions, we can provide support for people who have had past issues. If we can help them enrich their environment for themselves and for their children, it can really be helpful. Environmental enrichment is another form of epigenetic modification that may be able to reverse the developmental trajectory and contribute to normal healthy neurodevelopment. Im definitely on the side of compassion, enrichment, and social support, and I think that those things are going to be really important going forward.

Where is your research headed next? What other questions are you hoping to answer?

The research Im doing now is trying to look at the development from embryo, to prenatal pups, to postnatal day-one pups, and throughout development to see if we can figure out how the offspring rats are developing differently. That could help us understand why they would respond to these two drugs, opioids and cocaine, so differently.

If we can figure out the specific biological mechanisms by which such behaviors are transmitted from one generation to the next, then we can work to intervene medically, and well understand more about how evolutionary biology operates. Thats what will make our research more applicable to humans in the future.

If effects like you describe did leave a child predisposed to addiction, could you reverse that somehow, maybe with nurturing or environment?

What this research can tell us is that our environment can impact our offspring. All the experiences youre collecting throughout your life are changing your epigenetics, or the way that your offspring are going to develop. For the rats, the only thing that the male donates to the offspring is his sperm. He doesnt do any fathering. So, theres something in the sperm thats changed as a result of the previous drug exposure. We think these are epigenetic modifications.

For a long time, people thought an individuals genetics were responsible for everything. But even if you have the same genetics, your environmental experiences can change how you react to things and how your offspring are going to react to things. I also think some tendencies are going to be reversible. So just the same way that your own opioid use might change the way your offspring take drugs, if you provide lots of environmental enrichment, for example you read to your child every day, then that could change or mitigate some of the effects of your past opioid use. Environmental enrichment is beneficial for everyone and can be particularly helpful in providing a strong foundation for neurodevelopment of children.

Some peoples brains are going to be more vulnerable to addiction, and its a combination of environmental exposures and genetics. Its not a failure of morality. Understanding that this is not a choice, that its a disease, is important.

Angela Nelson can be reached atangela.nelson@tufts.edu.

See the original post here:
What Opioid Use in Rats Can Tell Us About Addiction in Humans - Tufts Now

Recommendation and review posted by Bethany Smith

Drug development is the process of bringing a novel drug from bench to bedside. It can take 10 to 15 years for a drug to be designed, developed and approved for use in patients (Fig 1). In some circumstances, the drug development and approval process can be expedited for example, if the drug is the first available treatment for a condition, or it shows a significant benefit over existing drugs.Before a drug can reach a patient, it must go through rigorous testing to determine whether it is safe, effective at treating the condition it was developed for, and to ascertain the correct dosage and appropriate administration route.

Pharmaceutical regulatory authorities are responsible for overseeing and regulating therapeutics; including prescription and over-the-counter drugs, vaccines, cell therapies, and medical devices. They play a key role throughout the drug development process and are designed to ensure the safety, efficacy, accessibility and security of approved drugs. Throughout the development of the drug, the responsible pharmaceutical company will conduct pharmacovigilance activities.

Numerous different regulatory authorities exist worldwide. The USAs regulatory agency is the US Food and Drug Administration (FDA) and the UK equivalent is known as the Medicines and Healthcare Regulatory Agency (MHRA) every country has its own regulatory authority.

2. Preclinical Research

3. Investigational New Drug Application

4. Clinical Research

5.Regulatory Review, Approval and Post-marketing Safety Surveillance

Figure 1: An overview of the drug discovery, development and approval process.

Numerous screening approaches can be used to identify a hit compound. A hit can be defined as a compound that interacts with the target of interest. There are several strategies that can be used to discover hits including; high-throughput screening, phenotypic screening, virtual screening, fragment-based screening and structure-based design.

In phenotypic screens, the specific drug target may not be immediately evident as the approach is based on determining if a compound exerts a desired effect by observing a change in phenotype. The target underlying the observed phenotypic change may be identified later although there isnt a regulatory requirement to know the target of a drug provided it demonstrates good safety and efficacy properties.

It is extremely important that the most appropriate animal model is used at this stage, as well as considering the gender of animals to be used to prevent sex-specific bias. A drug could elicit a different response in a male animal compared to a female. You will also need to consider species-specific physiology and similarities in terms of metabolic pathways and genetics (for example 99% of all mouse genes overlap with human ones).

An IND can be categorized as either commercial or research. For an IND application there are key areas that must be covered: animal model pharmacology and toxicology studies, manufacturing information, clinical study protocols and investigator information.The IND sponsor is required to wait 30 days before starting clinical trials this delayed period gives regulators the opportunity to review the information contained within the IND application.

The clinical stage of drug development follows a series of Phases.

Study length: Typically, several months.

Primary purpose: To determine safety in humans, and to gather information on dosage. Phase I studies also guide how best to administer the drugto limit toxicity and enhance therapeutic effectPhase IINumber of participants: Several hundred. The participants will be diagnosed with the condition/ disease you a re developing the drug to treat.Study length: Spans from several months to two years.

Primary purpose: To acquire additional safety data to determine efficacy and adverse effects. This information is used to optimize the design of the larger Phase III study.Phase IIINumber of participants: 300 3000. The participants will be diagnosed with the condition/disease you are developing the drug to treat.

Study length: Spans from one to four years in length.

Primary purpose: To determine the drugs efficacy and to monitor adverse reactions. Due to the increased number of participants during Phase III, long-term or rarer side effects that may have gone undetected in Phase I and Phase II are usually detected. The greatest proportion of safety information is collected during Phase III.

The regulatory authority is responsible for the scientific evaluation of the NDA or MAA. The goal of the application is to provide the regulator with enough information gathered during preclinical and clinical studies for them to be able to determine if:

Number of participants: Several thousand. The volunteers will be diagnosed with the condition/disease that the drug is approved to treat.

The purpose of a Phase IV study is to obtain additional information about the long-term risks and benefits of taking a drug now that it is being more widely used. The real-world data can also help determine if there is scope to develop the drug further, for example:

More:
Exploring the Drug Development Process - Technology Networks

Recommendation and review posted by Bethany Smith

"Long-term, ZED horseswill develop a genuine emotional life with owners and bettors, even interacting with augmentedand virtual reality to bring these horses to life!" says Unikrn's CEO.

United States | 03/11/2020

C

Advertising

ould you describe in detail what are the disruptive innovations this product is bringing to the gaming industry? What are your short and long-term prospects and expectations for it?

Until now, virtual horse racing is little more than a roulette machine with a poorly rendered, horse-themed loading bar. Thats enough for some bettors, but we know it can be much, much more. Unikrn and ZED are evolving the space by bringing all the key parts of real horse racing together into a single digital platform.You can now own, trade, breed and race digital thoroughbreds, each with its own uniquecharacteristics, history and statistics passed on through blockchain-based genetics. Take thehorse you own and make the horse of your dreams, win cash racing them in real digital contestsof speed and stamina.

A ZED race isnt a random number generator. Its a bet on something so close to real that youcan feel the sweat at the finish line. Unlike other horse races, ZED creates continuity andnarrative. In ZED, a racehorses history from its races to its breeding record to its preferredstarting gate carries with it from race to race. Short term, ZED will let anybody get into racing horses and build a community from an emergingdemographic to build the next wave of casual racing and gaming fans. Long-term, ZED horseswill develop a genuine emotional life with owners and bettors, even interacting with augmentedand virtual reality to bring these horses to life!

When is the first race set to debut? Will there be betting options 24/7/365? Howare these exactly?

After months of beta testing, ZED is preparing to launch races in 2020 with a USD 20,000 prize pool. A regulated betting launch on Unikrn will follow shortly after complete with a beautifulspectator experience.

Why have you chosen horse racing game ZED RUN for this launch, and whatdoes this imply? For how long have you been working on this product, and howwas the path leading to this launch?

Through centuries, ownership of a prize racehorse was a privilege for the super wealthy. ZED isbreaking down the barriers for owning, operating and enjoying horse racing - were making it funwithout all the work.

Could you delve further into the non-fungible token (NFT) standard the gamewill rely on? What features does this bring? Do you think this product could bea landmark and open doors for new synergies between blockchain and sportsbetting?

ZED uses the ERC-721 NFT standard, which means all horse data will be recorded on theblockchain that can be publicly cross-checked, such as a racehorses DNA, past performance,name, colour and its family tree. So basically were making it possible for users to openly viewall the horses available, make offers to breed, trade, and race their horses with or againstothers. Unikrn and ZED are hyper focused on moving horse racing into the future for now, but thistechnology could certainly change the future of sports in general.

How is the process through which users can breed horses from their ownstables? What are your expectations for this in particular?

Users can breed with their own stables by placing their male racehorse into the studmarketplace (excepting inbreeding, which isnt allowed). We anticipate a fine balance between auser breeding within their own stables and also in protecting its bloodline. Just like in real horseracing, we expect strong performance horses to fetch higher prices in the breeding market.

What are your strategies and resources to actually draw and combine twodifferent audiences, such as esports fans and horse bettors?

Esports fans arent only esports fans, thats why Unikrn offers esports betting, skill wagering, an online casino and even a traditional sportsbook Unikrn is a modern esports first entertainment HUB. We know from our sites usage that theres heavy crossover between these and other options, and we also know our audience is blockchain-interested (thats why we accept cryptocurrency deposits and bets). ZED is just a natural extension of what we already offer a superior experience revolutionizing what used to be the status quo.

Are you currently working on finding partnerships with US casinos forcompetitive betting? What are your goals and prospects in that area?

We are constantly being approached by a variety of traditional and digital entertainment providers, including casinos and even licensed venue operators. We have some very exciting announcements in the pipeline that will catapult ZED into the mainstream, which we will announce in due course.

Nearly a year ago you launched Unikrn Virtual, enabling eSports users to bet24/7 on top teams from past rounds competitions. Can we have yourassessment of that product so far, in terms of performance and feedback?

Unikrn Virtual is a 24/7 virtual esports feed. Since we launched, weve added in thousands of exclusive, never-before-seen contests featuring some of the best esports competitors in history. Fans love to come see our competitors, including all-time champions like Justin Wong and Perfect Legend, play exclusively against hand-picked opponents. You could sit and watch Unikrn Virtual for every waking hour over weeks and still see contests that surprise and excite you, betting on tens of thousands of options. People love it. We love it. Well be adding several new titles to Unikrn Virtual this quarter, all of which feature hand-picked professional players duking it out in exclusive rounds. Weve seen a lot of interest and were excited to push the boundaries of what a virtual bet can become.

See more here:
'Unikrn and ZED horse racing technology could certainly change the future of sports in general' - Yogonet International

Recommendation and review posted by Bethany Smith

CBD Cannabidiol (or cannabis)

Since CBD products hit the market, thousands of products hit the market, some good, some not good at all. If you are taking CBD, please check to see if your product meets label claims at CBDverify.com. To understand what they do when assaying products this is the assay of our 500 mg sleep CBD:

DESCRIPTION: PLANT HEALTH R.E.M. CBD

BOTTLE: 30 mil, 1 fl oz.

CBD CONTENT ON LABEL: 500 mg

RESULT: PASS

FINAL TEST RESULT

CBD TOTAL: 513.60 mg

CBG TOTAL: 3.04 mg

THC TOTAL: ZERO

Tetrahydrocannabinol (THC), the psychoactive part of the marijuana plant and it is in only one of our products, Pachamama, which comes from Colorado. It meets the federal regulations of the amount of THC allowed in a CBD product. For anyone who may be tested in the work force, I would not allow them to get this product.

We have within us an endocannabinoid system which is made up of two types of CBD receptors CBD 1 and CBD 2. CBD 1 receptors are highly concentrated in the brain and other parts of the body and CBD 2 receptors are in the immune system and in the periphery. There are studies on CBD for the treatment and prevention of cancer through the CBD 2 receptors, regulating immune function. Not only does the research show promise with CBD in cancer patients, it also can help with nausea that comes with cancer treatment and can improve appetite.

There is also research on Multiple Sclerosis and Alzheimers Disease showing that there are more CBD receptors than in patients without either condition. It is called a compensatory response, so that, if a person with these conditions takes CBD, there is a stronger cellular response to repair.

There are contraindications with using CBD listed below:

1. If you are on medications, CBD can compete for liver pathways, leading to higher levels of the medication in your system (consult your physician)

2. It can raise liver enzymes in certain individuals, not most though. I believe this to be in patients that take multiple medications, however it can also be from a CBD product that is not organic and has pesticides and other chemicals in it. The last thing we should do is take a product for our health that is not clean, otherwise we are poisoning ourselves.

In our clinic, I prescribe CBD mainly for sleep, anxiety and pain as when CBD locks into our receptors it induces rest and relaxation as well as acting as an anti-inflammatory agent. We only carry products that are clean, meet label claims and the ones that we consistently get good clinical responses from and they are listed below.

1. The first one by Plant Health, REM 500 we prescribe for sleep.

2. The second one by Plant Health, Nutritional Tincture 2000 mg is full spectrum used mostly for pain.

3. Valo product is a capsule with 25 mg of CBD and 1 mg of Melatonin (works amazing for sleep in most patients)

4. The last one in the picture is from Pachamama in Colorado, which contains an FDA approved amount of THC, is full spectrum and they target pain with pepper, sleep with valerian, anti-inflammatory with turmeric and more.

Our topical CBD from Plant Health works wonders for local pain. Due to the fact that many CBD products do not work, have contaminants and dont meet label claims, CBD gets a bad name. Please only use reputable products where you can see the third-party testing for purity. From there dosing depends upon your needs and everyone doses slightly different to titrate to their benefit.

Dr. Theresa Ramsey is a practicing physician, speaker, lifestyle expert, author of the best-selling book, Healing 101: A Guide to Creating the Foundation for Complete Wellness & a guest expert on Arizonas top morning television show, Your Life A to Z, as their Medical Expert since 2007. Selected as a Certified Hormone Specialist, serving both local and out of state patients as her approach is Evidence Based and her prescribing is like nobody else in the valley when it comes to Quality of Life Enrichment as well as significant Aging Risk Reduction. Most physicians and lay people are uneducated on the safety and necessity of supporting our aging process which is considered a deficient state. Her prescribing is risk free. Dr. Ramsey has also been chosen as one of Phoenix Magazines Top Doc, was chosen as the Natural Choice Awards winning (1) Top Naturopathic Physician, (2) Top Womens Health Specialist and (3) Top Best Holistic M.D. in 2012 and 2013. She is also an eHow health expert. Dr. Ramsey elegantly bridges the gap between Allopathic & Naturopathic medicine as she has worked as an RN for 10 years before pursuing her career as a physician and appreciates what both sciences have to offer. The 10 years that she worked as a Registered Nurse was in Heart Surgery and ICU and then transitioned into Functional Medicine in 1996. An understanding of the cause of dis-ease is paramount in her education and inspiration for those seeking disease prevention and reversal. Her focus in her clinical practice is in Preventive Aging with Bio-Identical Hormone Replacement Therapy. Her second book, The Hormone Book covers all of the rich history through research on HRT prescribing and is anticipated to be released in the fall of 2020. https://revitalizeparadisevalley.com/: 480.970.0077.

The rest is here:
Benefits and Risks of Using CBD Products | Your Life Arizona - AZFamily

Recommendation and review posted by Bethany Smith

On this page:BasicsHormone TherapyNon-estrogen OptionsPerimenopause TreatmentSex After MenopauseNatural RemediesHot Flashes

Menopause symptoms getting in the way of living? There used to be only two treatment options: hormone therapy, or Just Deal With It (official Rx name, obviously). Thats far from the case now. Read on to find the right menopause solutions tailored specifically for you. And if you dont want to treat menopause, you dont have to. It's a normal phase of life, and the remedies are here for you only if you want 'em.

Menopause affects everyone uniquely. Its possible you could be in the menopause minority and experience a gradual spacing out and then stop of your periods, wonder what all the fuss is about, and feel positively liberated that you no longer have to shell out for tampons.

Or you may be one of the women who has hot flashes and night sweats. You could experience vaginal pain and urinary symptoms. Or you might be surprised at just how much your moods seem to shift along with your body. All of these menopause experiences are completely normal, and all are related to the drop in (or erratic behavior of) the reproductive hormones estrogen and progesterone.

Once you begin experiencing menopausal symptoms, it helps to find a clinician who has been trained specifically in menopause, whether its your gynecologist, PCP, or even another specialist you see who has received the training, such as an oncologist or reproductive endocrinologist. Youre looking for a pro who has certification from The North American Menopause Society (NAMS). The group has a function on its website where you can type in your zip code to search for a NAMS certified medical practitioner (NCMP) in your area.

People tend to have strong preconceptions about hormone therapy, or HT (previously called hormone replacement therapy, or HRT). But a lot of them are based on an outdated study from the Womens Health Initiative conducted in 2002, which implied that women who were put on HT had higher rates of heart attack, stroke, and breast cancer.

Turns out, the average age of the women enrolled in that study when they started HT was 64, while the average age most women have menopause symptoms and seek treatment is in their early fifties.

In the 17 years since the WHI hubbub, numerous new studies and reviews have shown that the safety of HT depends on how old you are when you start the hormones, your personal family history and other medical conditions, and the strength of the dosage.

The best time to begin (any type of) HT? The first time your symptoms start bugging you. The current recommendation for women without contraindicationssuch as a history of breast or uterine cancer (estrogen can help some breast cancer cells grow)is to start as early as possible on the lowest effective dose, and stay on it for the shortest time necessary.

The sooner you start taking hormones, the less potential risks they carry; these vary depending on your medical history but can include an increased risk of certain cancers, blood clots, and heart disease. Start right as menopausal symptoms become bothersome, and those risks significantly drop for most women.

It also helps when the hormones are administered transdermally, in lower doses, such as through a patch or gel or vaginally. As opposed to oral hormones, this method of delivery keeps the effects localized and therefore less likely to substantially affect other parts and systems of the body.

This is particularly the case for women in their 60s or ten years post menopause: For them, docs typically recommend lower-dose or more localized HT (such as vaginal-specific options) or nonhormonal medications (scroll down to read about SERMs and SSRIs).

Your NAMS-certified physician will discuss your particular symptoms and risks before prescribing any medication.

She may come to the conclusion that HT is not right for you, if you have a family history of breast, uterine, or ovarian cancer or heart attacks or blood clotsor if you are already over the age of 59, when risks of certain cancers, blood clots, and heart disease increase.

If youre low-risk, there are a variety of HT options available, but dont try any (or any meno treatment, for that matter) without first discussing with your doctor what other meds youre on.

Forty percent of women have vaginal issues during menopause. Prepare for such delightful things as dryness, irritation, pain during sex or exercise, and having to pee frequently and often.

Your doctor can help you find the right low-dose hormone therapy, localized around the vagina, if you only have vaginal and urinary symptoms. These include:

If youre really super-duper lucky, youll get symptoms that are vaginal and beyond! Oh yay!

This could mean hot flashes, sleep issues, mood swings, or bone loss. If this is you, youll likely want hormone therapy that isnt localized to the vagina.

As with contraceptive hormones, choosing the right hormone delivery method for menopause often comes down to personal preference. Some women like a patch they dont have to reapply as often, while others can't stand something stuck to them and go instead with gels or pills. The goal is finding something that feels natural for you.

Transdermal estradiol estrogen patch. Stick this on your lower belly or upper butt and get on with your life. Sold by the brands Estraderm and Vivelle.

Transdermal estrogen gel. Rub this gel, sold under the brand name Divigel, into the skin of your thigh each day and ahhhh, relief. It comes in varying strengths so you can experiment with your doctor to find the lowest effective dose.

Steroidal vaginal cream. This is not technically estrogen, but steroids that stimulate the nerves in vaginal tissue to help with sexual arousal. Steroids are hormones that affect, signal to, and act as catalysts for other hormonesin this case, for estrogen.

Look for the brand Interosa (prasterone, also known as dehydroepiandrosterone, or DHEA). It may help with depression and bone loss prevention as well.

Unfortunately, this cream is still off limits for women who cannot take estrogen, such as breast cancer survivors or women with a family history of breast cancer. And it can have adverse interactions with most psychiatric medications, including SSRIs (Selective Serotonin Reuptake Inhibitors), antipsychotics, sedatives, anticonvulsants, and sedatives, as well as other hormones such as estrogen and testosterone.

Oral estrogen and progesterone. For some women who are experiencing a barrage of systemic symptoms, a combination of oral estrogen and progesterone can be #treatmentgoals. The progesterone balances out the higher estrogen dose, helping to counteract the estrogen-related risks mentioned above.

These oral hormones do carry a larger risk for women with contraindications (such as a family history of breast, uterine, or ovarian cancer) than transdermal and vaginal hormones, because they tend to be prescribed at a higher dosagebut it is still considered low for most women who do not have contraindications and begin HT early. Specifically, women who start and undergo these treatments between the ages of 50-59 have a low risk compared to those who take them later. If you continue using them after 59, you should come in for more checkups to be monitored by your doctor.

Systemic hormone therapy can also cause spotting after menopause. Still, if youre on it and notice vaginal bleeding, talk to your doctor to make sure there isnt another cause.

Bioidentical hormones are hormones that are chemically similar in structure to hormones that naturally exist within the body. FDA-approved hormones for HT are, for practical reasons, bioidenticalotherwise, they would not be effective, because they would not work in the body.

But its not a medical phrase; "bioidentical hormones is mostly a marketing term for unregulated hormone products without a prescription. For example: companies selling unregulated yam creams and pharmacists whipping up their own (a big no!) compounded hormones (see Any non-prescription menopause treatments I can try? for more deets).

Its being used in the same way wellness, food, and beauty companies have co-opted the term all natural: Both sound good but are essentially meaningless labels with no real scientific definition or basis.

In the case of hormones, choosing something because it says bioidentical can be quite risky. The dosage is unregulated, so you simply dont know what youre getting. In fact, the term irks many doctors, as patients come to them after trying bioidentical hormones from an unreputable place and experiencing negative results.

The takeaway: If hormones are not FDA-approved, they are dangerous, whether they are bioidentical or not. There is no situation in which you should get hormones without a prescription. Ask your doctor for the FDA-approved hormones that are right for you.

As weve mentioned, there are various reasons people arent able to use estrogen, including certain preexisting health conditions or a genetic predisposition to breast cancer. Here are the most common no-estrogen options.

A SERM acts like and redirects estrogen to parts of the body that need it (see: bones, uterus) but not to the breasts. It can be a boon for women concerned about osteoporosis, because SERMs can also redirect existing estrogen to the bones, where it can help to prevent bone loss.

Some SERMssuch as Nolvadex, Soltamox, Tamoxen, Tamofen, Emblon, and Tamosin (all tamoxifen), and Evista (raloxifene)are even prescribed for the prevention and treatment of breast cancer. So, in all, SERMS can be a good option for breast cancer survivors, those with a family history of BC, or if youre at a high risk for bone loss or osteoporosis.

These increase the amount of serotonin in the brain by blocking its reabsorption. Though the exact relationship between estrogen, serotonin, and hot flashes is still being investigated, we do know that estrogen boosts serotonin production. When serotonin drops in menopause as a result of decreased estrogen, SSRIs have been found to reduce hot flashes and night sweats that can accompany the estrogen/serotonin deficit. These can be good options for women without psychological concerns who dont want to go on HT.

But! If you are experiencing emotional as well as physical symptoms (thanks, Lady M!), the beauty of an SSRI is it can knock out both. Estrogen increases production of the feel-good neurotransmitter serotonin; as it drops, you can have a steep decline in feelings of well-being and contentment. Not to mention crappier sleep. There can also be emotional stress as related to issues with sex and self-image. Enter: an antidepressant.

Do know that many psychiatric medications get served with a steaming side of sexual issues (such as lack of libido), so many women combine one with a low-dose vaginal product (as opposed to just higher-dose systemic HT). Its a balancing act that your doctor can help guide you through. The goal: the fewest symptoms, the lowest risk of side effects, and the best quality of life overall.

Another class of antidepressants used to treat anxiety, SSNRIs increase not just serotonin in the brain but also norepinephrine. This latter neurotransmitter is linked to learning, attentiveness, emotions, and sleep.

These are non-SSRIs that are also commonly prescribed for women during menopause.

If you are in the perimenopause part of menopausea years-long phase before you hit full meno in which your periods start getting wonkyconsider the hormonal options below if you are experiencing:

Both options were going to tell you about tap into the hormone progesterone, which can lighten heavy bleeding, lessen the length of time your period lasts (if its become prolonged), and even out your hormone levels. That latter part? Stabilized hormones = less extreme mood swings and sleep disruption.

Why choose one over the other? Its just personal preference.

Chant it with us (and Obama): Yes, we can!

The best treatment for menopausal dryness, irritation, and pain is an FDA-approved, low-dose vaginal estrogen (ring, gel, cream, or tablet). See deets on this above, in the section hormone therapy for vaginal symptoms.

If your vagina feels irritated even when youre not having sex and youd rather not go on HT, or you want more soothing, theres such a thing as a vaginal moisturizer. Yep, its like a daily, over-the-counter moisturizer you put on your face when your skin is dry, only its specifically formulated for your vagina and vulva.

You can go with an over-the-counter vaginal moisturizer or a lubricant. Its fine to use lube as moisturizer, if you find one you like. For both, heres how to pick a good one:

The brands Ah! Yes and Good Clean Love make a variety of moisturizers and lubes in this sweet spot of osmolality and pH.

Also remember: Sex is not just intercourse. Give other stuff a try!

Use menopause as an opportunity to explore other types of intimacy and pleasure. Outercourseany foreplay and sexual activities not dependent on penetration as the main eventcan be revelatory for women at any age.

Like most OTC supplements and tinctures that claim to help with medical issues, those for menopause are running around like its the Wild West! Here are a few things to know:

Remember: The FDA does not regulate supplements that sell without a prescription. The North American Menopause Society (NAMS) recently did a full review of unregulated supplements currently being marketed specifically for menopause, with the conclusion that they all did more harm than good. Black cohosh (the root of an herb), for example, was found to be no more effective than a placebo, and in some cases even caused liver damage.

Any hormone-product that you can buy without a prescription is dangerous and unregulated, even if it is a natural cream, gel, spray, or pill.

There are also compounded hormonescombinations of various estrogens and sometimes other hormones, which are often DIY recipesmixed by pharmacists, doctors, or other people trying to profit on menopause.

Theyre not a good idea: They arent mixed in labs, arent regulated by the FDA, and some have been found to contain hugely varied estrogen amounts, many at dangerously high levels that could cause blood clot. Others have so little estrogen, theyre a waste of money.

There are some standard vitamins not specifically marketed as menopause supps but that can be beneficial during this time.

For example, magnesium has been shown to aid sleep, and calcium can protect against bone loss. Getting enough calcium as you age can help prevent osteopororis; this is because estrogen is an instigator of osteoblasts, the cells that build bone.

Both of these well-tested vitamins are safe to add to your regimen if you are having sleep issues or not getting enough calcium from food alone. Calm Plus Calcium, which comes in a drink or gummies you can take before bed, has both.

These dried, powdered mushrooms and other plants may help with focus, alertness, memory, and mood. They have not been shown to have any ill effects and even help some people cut down on caffeine (which can contribute to insomnia in menopause).

MUDWTR is a tea that is a mix of chai herbs and spices as well as adaptogenic mushrooms and plants including lionsmane, cordyceps, reishi, chaga, turmeric, and cacao.

With zero sugar and less caffeine than coffee, it is a safeand tasty!morning substitute that (because of the adaptogens) may also help with some menopausal symptoms, such as mood swings and brain fog, according to recent studies.

Ye olde weed may be a political lightning rod, but products containing its compounds are relatively safe sleep and sex abettors. The two main compounds in marijuana are:

Some people like cannabis for menopause because it has fewer dangerous side effects and contraindications and a lower risk of being addictive than many prescription drugs for sleep or sex problems.

The product options for both CBD and THC include:

If youre trying an edible or tincture for the first time, start with a small dose and see how you feel, whether it is THC, CBD, or a combination of the two. A vaginal lube or moisturizer with THC is unlikely to give you the giggles and the munchies; instead, itll feel slightly numbing, warm, or tingling, effects some women find help with arousal.

In states where marijuana is legal, you can find products with THC from companies such as Foria which will direct you to dispensaries and other suppliers in your state for purchase. For online CBD products, we like Lord Jones. Its CBD goodies are shippable to states even where marijuana is illegal.

If you dont need HT or other meds and are looking for help for mild or occasional flashes, your best bet is to chill out! Like, litrally (said with British accent). Get cool with the basics (drink ice water, sleeping with the windows open) or these six tricks, no Rx necessary.

No matter which menopause symptoms you experience, know that relief is available. That said, your body is experiencing a naturalwe repeat, naturalchange. We hope this guide helps you assess talking points when discussing treatment options with your doctor. And if you decide you want to embrace your symptoms sans-treatment, we salute you.

Menopause care is different than other types of womens health care, because it is less important that the doctor is an ob/gyn and more important that she has NAMS (North American Menopause Society) certification. (This doc could also be your primary care physician, fertility specialist, reproductive endocrinologist, or even your cancer specialist, for example.) Generally, doctors, including gynecologists, receive little to no menopause training in medical school. NAMS offers its own training and certification specifically for menopause; you can do a search on their site by zip code to find all of the NAMS certified physicians in your area.

It means hormones mixed together without any medical or regulatory supervision; even if done by a pharmacist or an entrepreneurial doctor, these are not FDA-regulated or -approved. Creams, gels, supplements, or any other product containing compounded hormones have been found to contain wildly varying amounts of estrogen, which is dangerous. Too much can cause blood clots and other avoidable health issues, and too little means theyre ineffective and a waste of moolah. FDA-approved prescription hormones are both safer and more affordable: Your doc will make sure the dosage is kept as low as possible, while your insurance will likely cover the cost.

The best way to get vitamins during menopause is through a balanced diet. However, if you are concerned that you may be lacking, have your doctor check your blood work to determine if there is something specific you need. Just feeling a little run down and want to make sure your bases are covered? The Smarty Pants brand of multivitamin gummies has a Masters variety for women over 50, whch contains an arsenal of energizing vitamins such as B and D that menopausal women sometimes lack, and which are often not found in basic multis. They also boast DHA, omega-3, and CoQ10 for heart health, vitamin K for bones, lutein for eyes, as well as your daily RDA of everything else youd expect in a good womens multi.

There are many cannabis solutions for sexual dysfunction, so you definitely dont have to start inhaling to get your groove back. First, lets clarify: THC is the psychotropic compound in marijuana that can make you high and only legal in certain states. CBD is the part of the plant that relaxes you, almost like a mild sedative, to help you get in a chill mood without the high. In states where marijuana is legal, you can find lube, vaginal moisturizers, and low-dose edibles with THC from the brand Foria. (A topical vaginal product with THC isnt likely to get you high; it should feel slightly numbing, warming, or tingling, which some women find helpful for arousal.) In states where marijuana is still illegal, you can find the same wide array of products with CBD only; check out the brand Lord Jones.

See the original post here:
Menopause Treatment: Hormone Therapy & Other Remedies - HealthCentral.com

Recommendation and review posted by Bethany Smith

"Develop a rational plan and then try not to dwell on all the possibilities."

By Dr. Yalda Safai

ABC News The World Health Organization just declared the novel coronavirus a pandemic.

In the past few weeks, weve seen schools closed, events canceled, transportation services halted and stores emptied of sanitation products. These disruptions are not caused by the outbreak itself but rather peoples response to the outbreak a public panic or mass hysteria.

When our wellbeing is endangered, we are easily influenced by behaviors of others who face similar endangerment, Dr. Shinwoo Kang, a psychiatrist in New York City, told ABC News. Although technological and social advances have allowed people to be better prepared, it has also created as much anxiety, amplified by incorrect statements or egregious opinions.

When panic is present, people tend to become doubtful, fearful, pessimistic. Panicked people subconsciously make reactionary decisions to avert risk without stopping to think about the consequences of their actions. We have witnessed this first hand residents stocking up on hand sanitizer, toilet paper and bleach in bulk, or hoarding face masks needed by hospitals for medical personnel despite repeated announcements from health agencies not to do so.

The massive stock market volatility of the last few weeks, including the worst week since the 2008 financial crisis, is another example.

A study from Oxford University published in the journal Nature Neuroscience helps explain what panic does to the human brain. Researchers found that when panic and anxiety are present, these stimuli create a glitch in the brains higher-order decision-making center. More simply said, anxiety and panic can cloud our judgment.

Individuals under high stress may struggle to gauge environmental cues that could help them avoid worse outcomes, according to the Oxford researchers.

Additionally, neuroscientists at the University of Pittsburgh have found that anxiety and panic disrupt neurons in the prefrontal cortex the area of the brain responsible for decision making and that can affect long-term planning, understanding rules, calculating the consequences of various risks and rewards, regulating emotions and problem solving.

Panic leads your brain to think with emotion rather than intellectual higher processes of your brain, said Mona Degan, a primary care physician in Los Angeles. This can lead to irrational decisions, especially if we are part of a large group of people trying to do the same thing, such as stocking up on household supplies, which leads to unnecessary shortages.

Panic prevention should be a crucial goal of emergency management, because panic is contagious and destructive.

Outbreaks from recent history have evoked similar responses, including Severe Acute Respiratory Syndrome (SARS) in 2002 and Middle East Respiratory Syndrome (MERS) in 2012.

So why does mass hysteria impede more appropriate responses to containment?

Anxiety triggers our bodies to go into flight-or-fight mode, a natural human response to danger, which in turn secretes cortisol, a stress hormone, Degan explained. When activated, stress hormones can hinder a persons immune system.

Excess anxiety also can affect other hormones, including adrenaline, said Dr. Alexander Sanchez, a psychiatrist in New York City.

This imbalance of hormones can lead to the areas [of the brain] responsible for making responsible decisions, like the prefrontal cortex, to lose function, Sanchez added. People lose sense of proportion and start to imagine the worst possible scenario, even if it is unlikely.

It also can lead to xenophobia and discrimination, even though, as Degan reminded us, This virus does not infect people based off race anyone is susceptible.

It is important to keep calm and act logically in the face of a potential crisis. Take a moment to take a deep breath, Sanchez said. Read the recommendations from a trustworthy news source, develop a rational plan and then try not to dwell on all the possibilities.

What you should do instead is all of the things that we know help people to relax in general: Get good sleep, eat well and exercise if you are healthy enough.

Yalda Safai M.D., M.P.H., is a psychiatry resident in New York City and a contributor to the ABC News Medical Unit.

Original post:
How to avoid panicking in coping with coronavirus outbreak - Abccolumbia.com

Recommendation and review posted by Bethany Smith

The World Health Organization just declared the novel coronavirus a pandemic.

In the past few weeks, weve seen schools closed, events canceled, transportation services halted and stores emptied of sanitation products. These disruptions are not caused by the outbreak itself but rather peoples response to the outbreak -- a public panic or "mass hysteria."

"When our wellbeing is endangered, we are easily influenced by behaviors of others who face similar endangerment," Dr. Shinwoo Kang, a psychiatrist in New York City, told ABC News. "Although technological and social advances have allowed people to be better prepared, it has also created as much anxiety, amplified by incorrect statements or egregious opinions."

When panic is present, people tend to become doubtful, fearful, pessimistic. Panicked people subconsciously make reactionary decisions to avert risk without stopping to think about the consequences of their actions. We have witnessed this first hand -- residents stocking up on hand sanitizer, toilet paper and bleach in bulk, or hoarding face masks needed by hospitals for medical personnel -- despite repeated announcements from health agencies not to do so.

Shelves of paper products sit nearly empty at a Target in Alexandria, Virginia, March 12, 2020.

The massive stock market volatility of the last few weeks, including the worst week since the 2008 financial crisis, is another example.

A study from Oxford University published in the journal Nature Neuroscience helps explain what panic does to the human brain. Researchers found that when panic and anxiety are present, these stimuli create a glitch in the brains higher-order decision-making center. More simply said, anxiety and panic can cloud our judgment.

Individuals under high stress may struggle to gauge environmental cues that could help them avoid worse outcomes, according to the Oxford researchers.

Additionally, neuroscientists at the University of Pittsburgh have found that anxiety and panic disrupt neurons in the prefrontal cortex -- the area of the brain responsible for decision making -- and that can affect long-term planning, understanding rules, calculating the consequences of various risks and rewards, regulating emotions and problem solving.

"Panic leads your brain to think with emotion rather than intellectual higher processes of your brain," said Mona Degan, a primary care physician in Los Angeles. "This can lead to irrational decisions, especially if we are part of a large group of people trying to do the same thing, such as stocking up on household supplies, which leads to unnecessary shortages."

Panic prevention should be a crucial goal of emergency management, because panic is contagious and destructive.

A woman covering her face walks down Whitehall, as a meeting takes place addressing the government's response to the coronavirus outbreak at Cabinet Office in London, March 12, 2020.

Outbreaks from recent history have evoked similar responses, including Severe Acute Respiratory Syndrome (SARS) in 2002 and Middle East Respiratory Syndrome (MERS) in 2012.

So why does mass hysteria impede more appropriate responses to containment?

"Anxiety triggers our bodies to go into flight-or-fight mode, a natural human response to danger, which in turn secretes cortisol," a stress hormone, Degan explained. When activated, stress hormones can hinder a person's immune system.

Excess anxiety also can affect other hormones, including adrenaline, said Dr. Alexander Sanchez, a psychiatrist in New York City.

"This imbalance of hormones can lead to the areas [of the brain] responsible for making responsible decisions, like the prefrontal cortex, to lose function," Sanchez added. "People lose sense of proportion and start to imagine the worst possible scenario, even if it is unlikely."

It also can lead to xenophobia and discrimination, even though, as Degan reminded us, "This virus does not infect people based off race -- anyone is susceptible."

"It is important to keep calm and act logically in the face of a potential crisis. Take a moment to take a deep breath," Sanchez said. "Read the recommendations from a trustworthy news source, develop a rational plan and then try not to dwell on all the possibilities.

"What you should do instead is all of the things that we know help people to relax in general: Get good sleep, eat well and exercise if you are healthy enough."

Yalda Safai M.D., M.P.H., is a psychiatry resident in New York City and a contributor to the ABC News Medical Unit.

See more here:
How to avoid panicking with coronavirus outbreak - ABC News

Recommendation and review posted by Bethany Smith

In India, one woman is diagnosed with breast cancer every four minutes, accounting for 25 to 32 percent of all female cancers across the country. Furthermore, only 60 percent of women who are treated for breast cancer, survive for at least five years post-treatment in India as compared to 89 percent in the US. While these statistics paint a grim picture, a Bengaluru-based startup, OncoStem, is trying to turn things around.

Dr Manjiri Bakre, has a postgraduate doctoral degree in cell biology, OncoStem was built with a vision to develop innovative and affordable tests to personalise cancer treatment.

Dr. Bakres earliest encounter with breast cancer was during her PhD days, when a friend was diagnosed. But since it was diagnosed early, the tumour could be removed. However, soon the cancer relapsed, and spread to multiple organs. It was so sudden; we tried helping by sending her for various therapies, even non-traditional ones, but nothing helped, she says.

The sudden demise of her friend got Dr Bakre thinking about why, despite early detection, so many patients like her friend were unable to survive? When the tumors are small and detected early, typically, such patients should be doing well, she says.

During this time, companies in the West were developing tests that could analyse tumor biology and determine the risk of relapse in patients with early-stage breast cancer. These tests could help personalise a patients treatment plan based on their individual risk of relapse.

However, since these tests were very expensive, Dr. Bakre approached doctors in India and pitched her idea of developing a home-grown and affordable version of a similar test, which eventually led to the birth of OncoStem in 2011.

OncoStems flagship product, CanAssist Breast, is a machine learning-based prognostic test that helps personalise treatment for early-stage breast cancer patients who are hormone receptor-positive (HR+) and HER2-negative. It took 7+ years to develop, validate and get international accreditations for CanAssist Breast before going to market.

CanAssist Breast analyses a patented combination of five biomarkers, digitises historical medical records of patients, feeds into an AI-algorithm and produces a risk score. This score is used to categorise patients based on the risk of cancer recurrence clearly as either 'low or high' with no grey area in between. Patients classified as low-risk can potentially avoid chemotherapy, its costs, and side-effects. CanAssist Breast is performed in OncoStem's NABL and CAP-accredited laboratory in Bangalore. The product is also CE marked.

If the patient is low-risk as per CanAssist Breast, they can avoid chemotherapy and in turn its associated side-effects and financial burden. Chemotherapy can affect multiple different body parts causing nausea, hair loss, infection, anemia, appetite changes, fatigue nerve and muscle problems, urinary bladder and kidney problems, and fertility problems. Febrile neutropenia, a life-threatening complication, is a serious side effect of many forms of chemotherapy.

CanAssist Breast makes customised treatment possible by analysing the patients tumor in depth, and providing a patient specific report indicating if the patient has low or high risk of cancer recurrence. This clear distinction of patients based on risk of cancer recurrence allows doctors to devise chemotherapy treatment in tune with the prognosis, maintaining a balance between the benefits and side effects.

Most tests available in the market that help decide if chemotherapy is required, are from the USA and in turn prohibitively expensive and not validated on Indian patients, Dr Bakre says, adding that CanAssist Breast, launched recently, is the only test validated on Indian patients and is also the most affordable option available currently anywhere in the world at 1/5th the cost of competing tests available in the US.

OncoStem performed a study which is published in Indian Journal of Surgical Oncology, to assess the impact of CanAssist Breast on treatment of early-stage breast cancer patients. In it, they found that CanAssist Breast helped 70 percent of early-stage breast cancer patients avoid chemotherapy. Not only did these patients avoid the physical hardship, but also the financial toxicity of chemotherapy. Moreover, with 93 percent of doctors complying with the test recommendation of avoiding chemotherapy, showed that physician confidence in the test is high.

Since its founding, OncoStem has grown leaps and bounds. Based in Bengaluru, Dr Bakre today has a team of 35 people, including Pathologists, scientists and statisticians, who worked on CanAssist Breast and continue to work on new products and a sales team spread across the country.

However, this upward trajectory had to overcome its share of challenges, particularly when it came to fundraising.

Finding space to set up her laboratory to get the deep science based R&D work going was also a tough task. After months of searching for the ideal space, her investors kindly offered to use part of their office space to set up the laboratory.

Next came the daunting task of working with hospitals and doctors, especially when the company had no track record. Convincing the doctors of the science was the key to get them interested in working with us. I must have approached 50-60 hospitals to work on developing and validating CanAssist Breast, which ultimately led to 10+ large hospitals signing up.

OncoStem's mission is optimising treatment for cancer patients and helping to avoid overtreatment. Dr Bakre says that every member of her team has had interactions with their user base, and has direct knowledge of what information doctors are looking to get from their test, how to improve the user experience, etc. We also are in constant touch with our patients to counsel them, explain the test and follow up on them. OncoStem wants real world evidence of how the test is performing. So they ask patients who took the test if their treatment was as per the test result (i.e no chemotherapy if they were low risk), and also how patients are faring. OncoStem uses this data to publish new clinical utility and decision impact studies.

In the near future, OncoStem plans to expand access to CanAssist Breast to South East Asia & Middle East, while working on the complete automation of CanAssist Breast so that it can be packaged as a Kit in the future. We are also working on developing new tests for two additional cancers and partnering with hospitals across India to clinically validate these tests. We currently have a solution for hormone-positive breast cancer that is already in the market and are working on another subtype of breast cancer as well as ovarian cancer, she concludes.

Read more here:
This diagnostics startup is revolutionising cancer treatment in India - YourStory

Recommendation and review posted by Bethany Smith

Photo: Philipp Nemenz | Getty Images

How to Boost Your Immune System During the Coronavirus Outbreak

The following article is written by Ben Angel. Author of the book, Unstoppable: A 90-Day Plan to Biohack Your Mind and Body for Success. Buy it now from Amazon | Barnes & Noble | iBooks | IndieBound. And be sure to order The Unstoppable Journal, the only journal of its kind based on neuroscience, psychology and biohacking to help you reach your goals.

As we all grow accustomed to life in the age of novel coronavirus COVID-19, and scientists continue working on antivirals and vaccines,many experts are suggestingthe public take a holistic approach to general health maintenance. And as biohackers know better than most, positiveimmune responsecan beessential to staying healthy.While the following suggestionsare not ways to prevent you from contracting the virus, they areeasyways to keep yourself as healthy as possible.

As noted in a recent studyfrom the Sleep Foundation, "Without sufficient sleep, your body makes fewer cytokines, a type of protein that targets infection and inflammation, effectively creating an immune response. Cytokines are both produced and released during sleep, causing a double whammy if you skimp on shut-eye. Chronic sleep loss even makes the flu vaccine less effective by reducing your bodys ability to respond."

onsequently, the study advises taking two 30-minute-or-less daily napsto help mitigatesleep deprivation's effects on the immune system. But if you're having a difficult time getting to sleep, you can try the many binaural beats found on YouTube (Jody Hattons Power Napsis a good place to start)to help grab some winks on your coffee break.

Getting rid of sugar biohacks your immune system by removing a food source for the bad bacteria in your gut that can kill off your good bacteria. Autoimmune problems anddigestive issues are telltale signs of gut imbalance. Ideally, your gut should be 85 percentgood bacteria or probiotics.

You can check for gut dysbiosis through gut-microbiome tests from companies like Thryve Inside, as well as take stock of what youre eating on a daily basis. Fermented foods like sauerkraut, kombucha and kimchi can all help repopulate the good bacteria in your gutas well, leaving you with more energy and vitality.

Its been known for centuries that fasting has been used as a health protocol. Paracelsus, a great healer in the Western tradition, wrote 500 years ago that,Fasting is the greatest remedy, the physician within. In 2014, Dr. Valter Longo of the University of Southern California discovered that fasting for threedays (having nothing but water) could essentially reset the immune system. As summarized on Humann.com, holding off on eating for at least 16-18 hours after your last meal allowsyour bodys attention to become "focused on the current immune cells, recycling them and getting rid of the damaged cells. This means that during the fast, your body is running lean and mean with its white blood cells."

This practice, of course, should only be done if youre already healthy. But provided that's the case, who wouldnt want more time to completeprojects at workand get healthier at the same time?

Stress causes an inflammatory response within the body that can greatly affect your fight-or-flight response by releasing too much of the stress hormone cortisol. It also leaves us more vulnerable to infections and disease, both in and out of the office. That's why mindfully meditating has become a must forany biohacking entrepreneurs. There arevarious forms of mindfulness practices, ranging from the slow-moving poses ofyoga and tai chi to myriad breathing techniques. And arecentstudyinTranslational Psychiatry adds that "there seems to be something intrinsic about meditation itself that can shift gene expression and even boost mood over time."

Many airlines are now monitoring travelers's health before and after flights. According to the CDC, those with no respiratory symptoms do not need to wear a medical mask. The CDC also recommends the use of masks for people who have symptoms of the virus and for those caring for individuals who have symptoms, such as cough and fever.

In his book, Cockpit Confidential, author Patrick Smithstates that in an airplane, Between 94 and 99.9 percent of airborne microbes are captured, and theres a total changeover of air every two or three minutes far more frequently than occurs in offices, movie theatersor classrooms.

This is all the more reason why taking your vitamins during stressful times is important, since many of our essential minerals and vitamins can become depleted during stress. Vitamins C,B and D, as well as zinc,all support your immune system. Research shows that zinc alone can help keep inflammation at bay so that your immune response is better supported.

Related: Coronavirus and a Looming RecessionHow to Raise Capital in Uncertain Times

Although we are in uncertain times, we dont have to wait to see if we are healthy enough to overcome any type of sickness or disease. By implementing some of these holistic steps to boost your immune system, it will inevitably be a win-win situation for not only your health and well-being, but for keeping your business running like a well-oiled machine.Bottom line: Dont panic, and take advice from the medical professionals who are specialists in this area.

This article solely reflects the opinion of the author and is not intended as an alternative to recommended official government guidelines. For more updates and information about the novel coronavirus, visit the CDC's website.

Are you ready to become unstoppable?

Visit http://www.areyouunstoppable.com and take your FREE 60-second online quiz now. By answering a series of simple questions, my software will analyze your results and provide you with a comprehensive report that will indicate your identity type and lead you to the tools and tips you need to close that gap between who you are and who you could be. Take the quiz to get started!

Related:Amazon Asks All Employees to Work From Home#4 Tips On How To Effectively Pitch Your Story To The Media HousesDelivery Apps, Ride Hailing Firms Call For Caution Amid Coronavirus Scare

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How to Boost Your Immune System During the Coronavirus Outbreak - Thehour.com

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Friday the 13th and Fear of Coronavirus: The Positive Mindset I Hope We'll Adopt

On average, there is a Friday the thirteenth every 212 days. Such a day occurs in any month that begins with a Sunday. Fear of this day has been given the scientific name, paraskevidekatriaphobia, from the Greek words for Friday, thirteen, and fear.

By contrast, we dont yet have a scientific name for fear of coronavirus, but that makes such fear no less real. Or less dangerous.

Sophie Trudeau, wife of the Canadian prime minister, has tested positive for coronavirus. The Capitol, White House, and Supreme Court have been closed to the public.

US stocks had their worst day since the 1987 stock market crash. The NCAA canceled its basketball tournaments for the first time in history. All eleven Disney theme parks in North America, Europe, and Asia have been closed. The PGA has canceled the Players Championship and the next three events on the schedule.

These are frightening days, indeed.

One psychologist notes, Fear influences how we react to media coverage of health hazards. In times of anxiety, we tend to pay more attention to threat-related information, which drives up our anxiety and distress.

This bias for threat can exacerbate our reaction to the disease, leading to panic. And panic is an irrational fear reaction that, by definition, your bodys reaction and adrenaline response take over from your ability to actually rationally evaluate the situation.

Responding appropriately to fear is therefore vital not just for our psychological wellbeing but for our physical health as well.

According to Cleveland Clinic, stress causes our bodies to produce greater levels of the hormone cortisol and can cause anxiety and depression. These can lead to elevated inflammation that can compromise our immune system.

Stress also decreases the bodys lymphocytesthe white blood cells that help fight infection. The lower our lymphocyte level, the more we are at risk for viruses such as SARS-CoV-2, the virus that causes COVID-19.

Since, as one professor notes, the main way we relate to information about the world is through feelings and gut intuitions, it is vital that we focus on objective medical advice and practical steps we can take today.

And it is vital that we turn to resources that can provide peace we cannot produce ourselves.

This week, weve focused on ways the Christian faith uniquely helps us in times of crisis such as the coronavirus pandemic. Weve discussed Jesus responses to our prayers, his invitation to trust him with our fears, the power that comes from submitting to the power of God, and the relevance and hope found in Christian community.

Unfortunately, many in our culture believe we have a binary choice: we can trust God or we can trust science, but we cannot do both. This is a false dichotomy.

Scientists use minds and abilities given to them by the God who calls us to steward his creation with excellence (Genesis 2:15; Philippians 4:8). Christianity has made dramatic contributions to the development of hospitals and the advancement of medical care.

According to a University of Chicago study, 76 percent of doctors say they believe in God and 55 percent say their religious beliefs influence their practice of medicine.

It is a mistake for scientists to discount Gods wisdom, just as it is a mistake for Christians to discount scientific wisdom. The Great Physician uses physicians in his continued ministry on earth.

In John 4, it says that Jesus had to pass through Samaria (v. 4). As you may know, Jews typically avoided Samaria on their way from Judea to Galilee and vice versa.

But Jesus went where other Jews would not go. In fact, had to translates a Greek word meaning must or to be necessary. Every time we find this word in Johns Gospel, it indicates divine direction and necessity (cf. 3:7, 14, 30; 9:4; 10:16; 12:34; 20:9).

Jesus had to pass through Samaria because his Father sent him to those who could not or would not come to him. Our Lord now continues his earthly ministry through us. We are his hands and feet, the physical expression of his spiritual presence (1 Corinthians 12:27).

As a result, here is the positive mindset I hope well adopt: lets join God as he is already at work in this crisis.

He calls physicians just as he calls pastors. He uses their expertise to advance his healing ministry in our broken world. Lets pray for them, encourage them, and follow their guidance.

In addition, he calls us to use our gifts, abilities, resources, and influence in proactive ways as he leads and empowers us. People may be more open to their need for God now than they were a month ago. They may be more aware of their mortality and limitations. They may be more willing to seek help. And they may be more open to our witness and compassion.

The coronavirus pandemic is indeed unique and frightening., but it also presents a unique opportunity to take Christ to our frightened culture. The God who redeems all he allows wants to redeem this physical threat for eternal spiritual good.

How can you join him today?

Publication date: March 13, 2020

Photo courtesy: Getty Images/Elena Volf

For more from the Denison Forum, please visit http://www.denisonforum.org.

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Friday the 13th and Fear of Coronavirus: The Positive Mindset I Hope We'll Adopt - Christianheadlines.com

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Varicose veins are incredibly common especially among adult women and they are also distinct in appearance: Blue, purple-tinted twists and turns underneath the skin, which usually take shape on the legs. For some people, varicose veins are merely a cosmetic issue (that can easily and quickly be fixed, thanks to advancing technologies and approvals by the Food and Drug Administration). While for others, the presence of these swollen, enlarged veins can bring on a host of painful side effects.

Here, we asked a handful of experts to explain everything about varicose veins, including what they are in the first place, why they form, and the potential risk factors that contribute to their development. If you're an adult of any age but especially if you've ever taken oral contraceptives this is what you need to know about varicose veins.

In simple terms, varicose veins are veins that become enlarged, twisted, and pooled with blood (which gives them their distinct bluish, purple-colored appearance). Technically speaking, "varicose veins are a condition where the deeper, large veins of the legs stop working normally and cause the vein to back up with blood, [thereby] becoming stretched out and dilated," explains George Skandamis, a board-certified dermatologist in Ohio.

The result of this backlog is swelling of the veins, which causes them to become visible on the surface of the skin. Varicose veins are often diagnosable simply by their appearance, although your doctor may use an ultrasound to confirm that the valves aren't working properly.

Varicose veins can range in severity from thin, threadlike veins (spider veins) to "deeper vessels called reticular veins which appear as medium-sized bluish veins under the skin," explains Laura Haygood, a board-certified dermatologist in Tyler, Texas. "The largest deep connecting varicose veins are not usually visible unless special ultrasound devices are used. " Varicose veins are most commonly found on the lower leg and inner thighs, as well as the shins, calves, and ankles (we'll explain why).

For some people, varicose veins are purely a cosmetic issue. For others, however, varicose veins can cause potentially debilitating physical symptoms like pain, aching, cramping, and restless legs. They might also cause the skin to become irritated or itchy, and some research suggests these symptoms can potentially worsen in warmer weather.

To understand what causes veins to become varicosed, it helps to first understand the body's venous system. Our veins, when functioning properly, operate as one-way streets: Moving blood from our peripheries (legs, arms, everywhere else) back to the heart.

Healthy veins "have little trap-door valves that don't allow blood to go backward," Skandamis explains. "When the vein is overworked from having to push blood up the body against gravity, the valves seals become leaky and blood is allowed to go backward, leading to the vein becoming enlarged."

This explains why varicose veins almost always occur on the legs because when we're standing or sitting, our veins have to work against gravity to do their job. "As gravity pulls everything down, veins tend to accumulate blood and it becomes harder for blood to travel upwards back towards the heart," says Danny Del Campo, a board-certified dermatologist in Chicago. "As time goes on, this backup of pressure leads to collapse of valves in the veins."

Varicose veins often develop as part of the aging process, after years of "increased venous pressure caused by standing or sitting in one position for prolonged periods," explains Haygood.

Other potential risk factors for developing varicose veins include, "family history, pregnancy, lack of exercise, and weight gain," she says.

Everyone, but especially those who are pregnant and/or have had more than one child, are at a higher risk for developing varicose veins than the general public. In fact, varicose veins affect nearly twice as many women as men, and spider veins may be an issue for half of all women, according to the U.S. Department of Health & Human Services Office on Women's Health. Why?

Read the rest here:
Varicose Veins: Everything You Need to Know About How They Form Expert Advice - Allure

Recommendation and review posted by Bethany Smith

New research has found that there are 362 cell and gene therapies in clinical pipelines in the US, an increase from 2018.

A new report from Americas Biopharmaceutical Companies has revealed that there are 362 cell and gene therapies in development in the US. Roughly a third of the therapies, 132, are potential treatments for rare diseases.

The research also highlights that the rate of R&D in this field is growing, as in 2018, a Pharmaceutical Research and Manufacturers of America (PhRMA) report on the cell and gene therapy pipeline found 289 therapies in clinical development in the US.

There are currently nine cell or gene therapy products approved by the US Food and Drug Administration (FDA).

Cell and gene therapies represent two overlapping fields of biomedical research with similar aims, which target DNA or RNA inside or outside the body. Gene therapies use genetic material, or DNA, to alter a patients cells and treat an inherited or acquired disease, whereas cell therapy is the infusion or transplantation of whole cells into a patient for the treatment of an inherited or acquired disease.

According to the report, the novel cell and gene therapies range from early to late stages of clinical development and are focused on a variety of diseases and conditions from cancer, genetic disorders and neurologic conditions.

Some of the cell and gene therapies in the pipeline include:

Another finding highlighted by the report is the 60 RNA therapeutics in development. Whilst not a kind of cell or gene therapy,RNA interference (RNAi) and antisense RNA use a genes DNA sequence to turn it off or modify the gene expression. So, these treatments can potentially inhibit the mechanism of disease-causing proteins.

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Almost 400 cell and gene therapies in US pipeline, finds report - European Pharmaceutical Review

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Barth syndromeis a rare metabolic disease caused by mutation of a gene calledtafazzinorTAZ. It can cause life-threatening heart failure and also weakens the skeletal muscles, undercuts the immune response, and impairs overall growth. Because Barth syndrome is X-linked, it almost always occurs in boys. There is no cure or specific treatment.

In 2014, to get a better understanding of the disease,William Pu, MD, and colleagues at Boston Childrens Hospital collaborated with the Wyss Institute to create a beatingheart on a chip model of Barth syndrome. The model used heart-muscle cells with theTAZmutation, derived from patients own skin cells.It showedthatTAZis truly at the heart of cardiac dysfunction: the heart muscle cells did not assemble normally, mitochondria inside the cells were disorganized, and heart tissue contracted weakly. Adding a healthyTAZgene normalized these features, suggesting that gene replacement therapy could be a viable treatment.

But to fully capture Barth syndrome and its whole-body effects, Pu and colleagues needed an animal model. The animal model was a hurdle in the field for a long time, says Pu, director of Basic and Translational Cardiovascular Research at Boston Childrens and a member of the Harvard Stem Cell Institute. Efforts to make a mouse model using traditional methods had been unsuccessful.

As described in the journalCirculation Research, most mice with the whole-bodyTAZdeletion died before birth, apparently because of skeletal muscle weakness. But some survived, and these mice developed progressive cardiomyopathy, in which the heart muscle enlarges and loses pumping capacity. Their hearts also showed scarring, and, similar to human patients with dilatedcardiomyopathy, the hearts left ventricle was dilated and thin-walled.

Mice lackingTAZjust in their cardiac tissue, which all survived to birth, showed the same features. Electron microscopy showed heart muscle tissue to be poorly organized, as were the mitochondria within the cells.

Pu, Wang, and colleagues then used gene therapy to replaceTAZ, injecting an engineered virus under the skin (in newborn mice) or intravenously (in older mice). Treated mice with whole-bodyTAZdeletions were able to survive to adulthood.TAZgene therapy also prevented cardiac dysfunction and scarring when given to newborn mice, and reversed established cardiac dysfunction in older mice whether the mice had whole-body or heart-onlyTAZdeletions.

Thats where the challenge will lie in translating the results to humans. Simply scaling up the dose of gene therapy wont work: In large animals like us, large doses risk a dangerous inflammatory immune response. Giving multiple doses of gene therapy wont work either.

The problem is that neutralizing antibodies to the virus develop after the first dose, says Pu. Getting enough of the muscle cells corrected in humans may be a challenge.

Another challenge is maintaining populations of gene-corrected cells. While levels of the correctedTAZgene remained fairly stable in the hearts of the treated mice, they gradually declined in skeletal muscles.

The biggest takeaway was that the gene therapy was highly effective, says Pu. We have some things to think about to maximize the percentage of muscle cell transduction, and to make sure the gene therapy is durable, particularly in skeletal muscle."

Reference: Wang et al. (2020).AAV Gene Therapy Prevents and Reverses Heart Failure in A Murine Knockout Model of Barth Syndrome.Circulation Research.https://www.ahajournals.org/doi/abs/10.1161/CIRCRESAHA.119.315956.

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Gene Therapy Reverses Heart Failure in Mouse Model - Technology Networks

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News Release

Monday, March 9, 2020

New strategy could be applied to other infectious diseases.

A new approach to direct the body to make a specific antibody against HIV led to sustained production of that antibody for more than a year among participants in a National Institutes of Health clinical trial. This drug-delivery technology uses a harmless virus to deliver an antibody gene into human cells, enabling the body to generate the antibody over an extended time. With further development, such a strategy could be applied to prevent and treat a wide variety of infectious diseases, according to the study investigators.

Researchers from NIHs National Institute of Allergy and Infectious Diseases (NIAID) reported the findings on March 9 in an oral presentation at the 2020 Conference on Retroviruses and Opportunistic Infections (CROI).

Antibodies are immune system proteins that help prevent or clear infections. Traditional vaccines induce the immune system to generate protective antibodies. Another approach to preventing infections is to deliver monoclonal antibodies preparations of a specific antibody designed to bind to a single target directly into people. Monoclonal antibodies also are used therapeutically, with many already approved for treating cancer, autoimmune diseases and other conditions and others being evaluated for treatment of infectious diseases, such as Ebola virus disease.

Administering proteins to people requires periodic injections or infusions to retain protective or therapeutic levels, which can be challenging, particularly in resource-limited settings. Delivery of antibody genes using a virus as a carrier, or vector, offers a potential alternative.

Monoclonal antibodies hold enormous promise for preventing and treating both established and emerging infectious diseases, said NIAID Director Anthony S. Fauci, M.D. Novel delivery platforms such as viral vectors could facilitate the future development and deployment of antibody-based prophylaxis and therapy, and these findings are a promising first step in that direction.

The drug-delivery system developed by scientists at NIAIDs Vaccine Research Center (VRC) uses adeno-associated virus serotype 8 (AAV8) to deliver an antibody gene. AAVs small viruses that do not cause disease in humans have proven to be safe, well-tolerated vectors for gene therapy. In a previous study in animal models, VRC researchers found that using AAV8 to deliver genes for antibodies against simian immunodeficiency virus (SIV), the monkey equivalent of HIV, led monkeys to safely produce high levels of anti-SIV antibodies and protected them from acquiring SIV.

Building on this preclinical work, researchers designed a Phase 1 clinical trial known as VRC 603. It aims to assess the safety and tolerability of an AAV8 vector carrying an anti-HIV antibody gene in adults living with well-controlled HIV, and to evaluate whether it could cause human cells to produce the antibody. The vector carries the gene for an anti-HIV monoclonal antibody called VRC07, which was originally isolated from the blood of a person with HIV.

VRC07 is a broadly neutralizing antibody (bNAb), meaning it can stop a wide range of HIV strains from infecting human cells in the laboratory. Other clinical studies are underway to determine whether bNAb infusionscan protecthumansfrom acquiring HIV. Scientists also are evaluating whether combinations of HIV bNAbs can suppress the virus in people living with HIV.

The CROI presentation by Joseph P. Casazza, M.D., Ph.D., principal investigator of VRC 603, described initial results from the first eight participants in the ongoing trial, which is being conducted at the NIH Clinical Center in Bethesda, Maryland. Each of these individuals, aged 30 to 60 years, received a single dose by intramuscular injection of one of three different dose levels of AAV8-VRC07. They continued taking daily antiretroviral therapy.

Following injection with AAV8-VRC07, all eight participants produced VRC07 at levels detectable in the blood. VRC07 production reached an early peak four to six weeks after injection, then decreased, and slowly began to increase again roughly 16 weeks after the injection. The researchers have monitored the five participants who received low or intermediate AAV8-VRC07 doses for one and a half to two years. For three of these five individuals, antibody levels one year after injection were higher than those observed at four to six weeks. The three volunteers who received the highest AAV8-VRC07 dose have so far been monitored for five months to one year. Two produced VRC07 at concentrations higher than those seen in the low and intermediate dose groups.

Study participants have not experienced any major side effects due to AAV8-VRC07. Some volunteers experienced transient mild tenderness at the injection site or mild muscle pain.

To the best of our knowledge, this marks the first time that an AAV-based technology to deliver an antibody gene has resulted in safe and sustained levels of that antibody in blood, said NIAID VRC Director John Mascola, M.D. We hope that further development of this technology will yield a drug-delivery strategy applicable to a broad range of infectious diseases.

Administration of monoclonal antibody-based therapies sometimes results in a persons immune system developing antibodies against the therapy. Only three of the eight VRC 603 participants developed antibodies against VRC07; it is not yet clear whether these anti-drug antibodies could reduce VRC07s ability to neutralize HIV. The VRC 603 participants HIV was kept under control with continued antiretroviral therapy during the trial.

The concentrations of VRC07 observed in the study participants were lower than the antibody concentrations observed in animal studies of the AAV8-based technology. The VRC researchers are analyzing data from VRC 603 to better understand the factors that determine how much bNAb is produced by human cells. They also are continuing to monitor the VRC 603 participants and to enroll new volunteers into the trial.

AAV8-VRC07 was developed by VRC scientists in collaboration with David Baltimore, Ph.D., of the California Institute of Technology and Alejandro Balazs, Ph.D., of the Ragon Institute of MGH, MIT and Harvard. AAV8-VRC07 was manufactured by the Clinical Vector Core of the Center for Cellular and Molecular Therapeutics at the Childrens Hospital of Philadelphia. More information about the VRC 603 trial is available on ClinicalTrials.gov using identifier NCT03374202.

NIAID conducts and supports research at NIH, throughout the United States, and worldwide to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.

About the National Institutes of Health (NIH):NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIHTurning Discovery Into Health

JP Casazzaet al. Durable HIV-1 antibody production in humans after AAV8-mediated gene transfer. Oral presentation at the 2020 Conference on Retroviruses and Opportunistic Infections (CROI). Presented March 9, 2020.

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Drug-delivery technology leads to sustained HIV antibody production in NIH study - National Institutes of Health

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HORAMA, a clinical stage gene therapy company in ophthalmology, today announced that Rodolphe Clerval has been appointed as Chief Business Officer (CBO). Rodolphe has a strong track record of executing strategic partnerships, business development deals and financing efforts. He will be responsible for business and corporate development, supporting HORAMA in operating a portfolio of gene therapy programs in inherited retinal dystrophies.

We are delighted to welcome Rodolphe, who brings us solid international experience in business development and corporate development strategy, acquired in biotech and pharmaceutical companies. His precious skills will allow us to prepare the next steps and to optimize the potential of our gene therapy products in ophthalmic diseases, for which there is a strong and unmet medical need , says Christine Placet, CEO, HORAMA.

Rodolphe Clerval (44) has over 18 years international experience in the pharma and biotech industry. Prior to joining HORAMA, Mr. Clerval was co-founder and Chief Business Officer at Enterome. During his tenure at Enterome, he has executed over 15 transactions, including major industrial partnerships with Takeda, J&J, BMS, Abbvie and Nestle Health Sciences, totalizing over 100m in upfront and R&D payments and in equity investments. He was also actively involved in fundraising rounds. Rodolphe previously worked with TcLand Expression and Genzyme in business development, and with Natixis as sell-side equity analyst. He started his career at Aventis Animal Nutrition as a scientist.

Rodolphe graduated with a degree in Biochemical Engineering from Polytech Marseille and he is a Certified European Financial Analyst from EFFAS/SFAF.

"HORAMA is a remarkable company, combining top gene therapy research, clinical stage programs with a strong team of industry leaders. I am thrilled to join HORAMA and to support the company in delivering best-in-class therapies in inherited retinal dystrophies", said Rodolphe Clerval, CBO, Horama.

Gene therapy market (source: FiorMarkets and Grand View Research, Inc)

Gene therapy is being developed with an aim to treat rare conditions with limited or no treatment options.Genetic disorders occur due to gene mutations, which can result in incorrect protein synthesis. Gene therapy is used to introduce a healthy gene into cells to allow the synthesis of a functional protein. Growing awareness and acceptance of gene therapy for various disease treatments are favouring market growth.The global gene therapy market is estimated to reach $5.5 billion by 2026, while the global ophthalmology market is projected to grow to $43 billion by 2026 (April 2019 report issued by Grand View Research, Inc.).

About HORAMA

At HORAMA, we believe in gene therapy to treat a broad range of inherited disorders.Our focus is on Inherited Retinal Dystrophies with our lead clinical program targeting patients with PDE6B gene mutations, a condition which leads to progressive vision loss in children and adults leading to legal blindness.Our team is pushing the boundaries of gene therapy by advancing next generation delivery platforms that will improve effectiveness and coverage of gene transfer to address multiple diseases. For more information, please go to: http://www.horama.fr.

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Contacts

HORAMA Christine Placet c.placet@horama.fr

Press: ALIZE RP Caroline Carmagnol Tel: +33 (0)6 64 18 99 59caroline@alizerp.com

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HORAMA Strengthens Its Management Team With the Appointment of Rodolphe Clerval as Chief Business Officer (CBO) - Yahoo Finance

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DetailsCategory: DNA RNA and CellsPublished on Friday, 13 March 2020 09:52Hits: 219

HAIFA, Israel I March 12, 2020 I HAIFA, Israel, March 12, 2020 - Pluristem Therapeutics Inc. (Nasdaq:PSTI) (TASE:PSTI), a leading regenerative medicine company developing a platform of novel biological products, today announced it has signed a collaborative agreement with the BIH Center for Regenerative Therapy (BCRT) and the Berlin Center for Advanced Therapies (BeCAT) at Charite University of Medicine Berlin to expand its existing framework and research agreement and conduct a joint project evaluating the therapeutic effects of Pluristems patented PLX cell product candidates for potential treatment of the respiratory and inflammatory complications associated with the COVID-19 coronavirus.

PLX cells are allogeneic mesenchymal-like cells that have immunomodulatory properties that induce the immune systems natural regulatory T cells and M2 macrophages, and thus may prevent or reverse the dangerous overactivation of the immune system. Accordingly, PLX cells may potentially reduce the fatal symptoms of COVID-19 induced pneumonia and pneumonitis. Previous pre-clinical findings of PLX cells revealed significant therapeutic effects in animal studies of pulmonary hypertension, lung fibrosis, acute kidney injury and gastrointestinal injury which are potential complications of the severe COVID-19 infection. Clinical data using PLX cells demonstrated the strong immunomodulatory potency of PLX cells in patients post major surgery. Taken together, PLX cells potential capabilities with the safety profile observed from clinical trials involving hundreds of patients worldwide potentially position them as a therapy for mitigating the tissue-damaging effects of COVID-19.

The collaboration with Charit researchers will allow us to expedite our program to potentially enable the use of PLX cells to treat patients infected with COVID-19 that have respiratory and immunological complications. The fact that PLX is available off-the-shelf, combined with our ability to manufacture large scale quantities, is a key advantage in case a large number of patients may need respiratory support. The primary target is to prevent the deterioration of patients towards Acute Respiratory Distress Syndrome (ARDS) and sepsis. We intend to start the joint collaboration immediately, with an aim to bringing much needed treatment to a rapidly expanding global health threat, stated Yaky Yanay, Pluristem President and CEO.

Prof. Hans-Dieter Volk, Director of the BCRT at Charite University Medicine Berlin, commented, Through our long-term collaboration with Pluristem, we have a thorough understanding of PLX cells and their mechanism of action. Charites unique knowledge, which includes research and clinical expertise in the immunopathogenesis of viral infections and critically ill patients, provides us an accelerated framework in which we believe PLX cells can be explored as a potential therapy for patients infected with COVID-19.

About BIH Center for Regenerative TherapiesThe BIH Center for Regenerative Therapies (BCRT) is a cooperative translational research institution of the Charit University Hospital in Berlin and the Berlin Institute of Health (BIH). The mission of the BCRT is to develop a translational platform for Regenerative Therapies from bench-to-bedside. The clinical platforms -- Immune, muskuloskleletal, and cardiovascular system -- are cross-linked by cross-field clinical fields (cachexia/sarcopenia, genetic diseases) and technology and translation support platforms. There are extended experiences in clinical trials with cell therapy, including phase 1-3 trials with PLX cells.

About Berlin Center for Advanced Therapies (BeCAT)The Berlin Center for Advanced Therapies is a spin-off of the BCRT focusing on translation of cell and gene therapies in the major research fields of regenerative medicine and cancer. It consists of four research fields (endogenous regeneration, tissue engineering, anti-cancer immunotherapy, and rare diseases) and three technology platforms (manufacturing, product characteristics and biomarker, and clinical development and regulatory affairs.

About Pluristem TherapeuticsPluristem Therapeutics Inc. is a leading regenerative medicine company developing novel placenta-based cell therapy product candidates. The Company has reported robust clinical trial data in multiple indications for its patented PLX cell product candidates and is currently conducting late stage clinical trials in several indications. PLX cell product candidates are believed to release a range of therapeutic proteins in response to inflammation, ischemia, muscle trauma, hematological disorders and radiation damage. The cells are grown using the Company's proprietary three-dimensional expansion technology and can be administered to patients off-the-shelf, without tissue matching. Pluristem has a strong intellectual property position; a Company-owned and operated GMP-certified manufacturing and research facility; strategic relationships with major research institutions; and a seasoned management team.

SOURCE: Pluristem Therapeutics

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Pluristem and Charit University of Medicine Berlin Join Forces Targeting Potential Treatment for Respiratory and Inflammatory Intratissue...

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Myst Therapeutics (Myst), a preclinical stage biotechnology company focused on developing selected TIL-based autologous T cell therapy products for cancer, announced the appointment of five leading experts in the areas of immunotherapy, tumor infiltrating lymphocytes, gene therapy, and oncology diagnostics to its Scientific Advisory Board.

"Myst is fortunate to attract these world-leading immunotherapy and cancer researchers to our advisory board," said TJ Langer, President and Chief Executive Officer of Myst. "Their experience and insight will be invaluable for the development and progression of our PuriT product pipeline."

James Mul, Ph.D. - Senior Member, Associate Center Director, and Michael McGillicuddy Endowed Chair in Melanoma Research/Treatment at Moffit Cancer Center. Dr. Mul has pioneered immune cell-based therapies and ushered them from the laboratory through Phase I and II clinical trials. He also leads work to engineer improvements to cell-based therapies through manipulation of tumor microenvironment and immune biological processes. Dr. Mul received his Ph.D. at the Fred Hutchinson Cancer Research Center, and fellowship training at the National Cancer Institute.

Michael Lotze, M.D. - Professor of Surgery, Immunology, and Bioengineering, University of Pittsburgh School of Medicine; Vice Chair of Research, Department of Surgery; Associate Director for Strategic Partnerships, University of Pittsburgh Cancer Institute; Asst. Vice Chancellor, UPSHS. Michael Lotze has been a forerunner in immune-oncology and gene therapy for three decades. He initiated the first gene therapies at the NIH and has treated over 100 patients at the University of Pittsburgh. He is a co-inventor on 10 patents, has authored over 500 scientific papers, and published numerous books and chapters on tumor biology and immunology. Dr. Lotz is the former CSO of Lion Biotechnologies (now Iovance Biotherapeutics).

Pamela Ohashi, Ph.D. - Co-Director of the Campbell Family Institute for Breast Cancer Research, Senior Scientist at the Princess Margaret Cancer Centre, Professor in the Departments of Medical Biophysics and Immunology at the University of Toronto, and the Director of the Tumor Immunotherapy Program at the Princess Margaret Cancer Centre. Dr. Ohashi is an expert on T cell behavior in the tumor microenvironment where her work has contributed to numerous Phase I and Phase II clinical trials. Dr. Ohashi is the author of over 150 scientific publications and has received numerous awards, including the American Association of Immunologists Pharmingen Investigator Award and the National Cancer Institute of Canadas William E. Rawls Award.

Chantale Bernatchez, Ph.D. - Associate Professor, Department of Melanoma Medical Oncology - Research, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX. Dr. Bernatchez is the director of the MD Anderson TIL Laboratory, where she leads the development of tumor infiltrating lymphocyte-based therapies. She currently supports a major Phase II clinical trial in Stage IV melanoma patients, the first of its kind outside of the National Cancer Institute, and is planning future trials utilizing novel techniques for promoting T cell survival and anti-tumor activity. Chantale received her Ph. D. from Laval University, Quebec and conducted postdoctoral training at both Laval University and MD Anderson Cancer center.

Alex Aravanis, M.D., Ph.D. - Dr. Aravanis is the Chief Scientific Officer, Head of R&D, and Co-Founder at GRAIL, the leader in early cancer detection diagnostics, and is commanding one of the largest clinical study programs in genomic medicine. Previously, Alex was Senior Director, R&D for Illumina, where he developed clinical assays for RNA and DNA analysis from fixed tissues, whole exome analysis, massively parallel single cell transcriptomics, and liquid biopsy using cell-free nucleic acids. Dr. Aravanis served as Vice President of Development and Chief Science Officer of Sapphire Energy Inc. and was a Co-Founder and Vice President of Engineering of Pria Diagnostics, LLC. Alex holds a PhD in Electrical Engineering, and an MD from Stanford University.

"These superb researchers are recognized for their significant discoveries and contributions in the field of tumor immunology and immunotherapy," stated James Mul, Ph.D., Associate Center Director and Michael McGillicuddy Endowed Chair in Melanoma Research and Treatment at Moffitt Cancer Center. "Their extensive experience in this field will be invaluable to Myst as the company advances its immunotherapy products to the marketplace."

Story continues

About the PuriT Platform

Clinical evidence has demonstrated that a patients' tumor infiltrating lymphocytes (TIL) recognize tumor specific molecules, traffic to the tumor, respond to tumor antigen, and selectively eradicate tumors. Clinical studies using these cells have shown durable objective clinical responses in patients with advanced metastatic disease, including refractory melanoma, breast, cervical, and colorectal cancer. Mysts PuriT platform builds on these successes by enriching and rejuvenating TIL to further improve responses. These encouraging results highlight PuriT as an emerging modality capable of providing personalized therapy options for patients spanning a broad spectrum of cancers.

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Contacts

Myst TherapeuticsTJ Langertj@mysttherapeutics.com

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Myst Therapeutics Appoints Leading Cancer Immunotherapy Experts to Its Scientific Advisory Board - Yahoo Finance

Recommendation and review posted by Bethany Smith

Mar 12th 2020

BEING ABLE to see all the details of the genome at once necessarily makes medicine personal. It can also make it precise. Examining illness molecule by molecule allows pharmaceutical researchers to understand the pathways through which cells act according to the dictates of genes and environment, thus seeing deep into the mechanisms by which diseases cause harm, and finding new workings to target. The flip side of this deeper understanding is that precision brings complexity. This is seen most clearly in cancer. Once, cancers were identified by cell and tissue type. Now they are increasingly distinguished by their specific genotype that reveals which of the panoply of genes that can make a cell cancerous have gone wrong in this one. As drugs targeted against those different mutations have multiplied, so have the options for oncologists to combine them to fit their patients needs.

Cancer treatment has been the most obvious beneficiary of the genomic revolution but other diseases, including many in neurology, are set to benefit, too. Some scientists now think there are five different types of diabetes rather than two. There is an active debate about whether Parkinsons is one disease that varies a lot, or four. Understanding this molecular variation is vital when developing treatments. A drug that works well on one subtype of a disease might fail in a trial that includes patients with another subtype against which it does not work at all.

Thus how a doctor treats a disease depends increasingly on which version of the disease the patient has. The Personalised Medicine Coalition, a non-profit advocacy group, examines new drugs approved in America to see whether they require such insights in order to be used. In 2014, it found that so-called personalised medicines made up 21% of the drugs newly approved for use by Americas Food and Drug Administration (FDA). In 2018 the proportion was twice that.

Two of those cited were particularly interesting: Vitrakvi (larotrectinib), developed by Loxo Oncology, a biotech firm, and Onpattro (patisiran), developed by Alnylam Pharmaceuticals. Vitrakvi is the first to be approved from the start as tumour agnostic: it can be used against any cancer that displays the mutant protein it targets. Onpattro, which is used to treat peripheral-nerve damage, is the first of a new class of drugssmall interfering RNAs, or siRNAsto be approved. Like antisense oligonucleotides (ASOs), siRNAs are little stretches of nucleic acid that stop proteins from being made, though they use a different mechanism.

Again like ASOs, siRNAs allow you to target aspects of a disease that are beyond the reach of customary drugs. Until recently, drugs were either small molecules made with industrial chemistry or bigger ones made with biologynormally with genetically engineered cells. If they had any high level of specificity, it was against the actions of a particular protein, or class of proteins. Like other new techniques, including gene therapies and anti-sense drugs, siRNAs allow the problem to be tackled further upstream, before there is any protein to cause a problem.

Take the drugs that target the liver enzyme PCSK9. This has a role in maintaining levels of bad cholesterol in the blood; it is the protein that was discovered through studies of families in which congenitally high cholesterol levels led to lots of heart attacks. The first generation of such drugs were antibodies that stuck to the enzyme and stopped it working. However, the Medicines Company, a biotech firm recently acquired by Novartis, won approval last year for an siRNA called inclisiran that interferes with the expression of the gene PCSK9thus stopping the pesky protein from being made in the first place. Inclisiran needs to be injected only twice a year, rather than once a month, as antibodies do.

New biological insights, new ways of analysing patients and their disease and new forms of drug are thus opening up a wide range of therapeutic possibilities. Unfortunately, that does not equate to a range of new profitable opportunities.

Thanks in part to ever better diagnosis, there are now 7,000 conditions recognised as rare diseases in America, meaning that the number of potential patients is less than 200,000. More than 90% of these diseases have no approved treatment. These are the diseases that personalised, precision medicine most often goes after. Nearly 60% of the personalised medicines approved by the FDA in 2018 were for rare diseases.

Zolgensma is the most expensive drug ever brought to market.

That might be fine, were the number of diseases stable. But precision in diagnosis is increasingly turning what used to be single diseases into sets of similar-looking ones brought about by distinctly different mechanisms, and thus needing different treatment. And new diseases are still being discovered. Medical progress could, in short, produce more new diseases than new drugs, increasing unmet need.

Some of it will, eventually, be met. For one thing, there are government incentives in America and Europe for the development of drugs for rare diseases. And, especially in America, drugs for rare diseases have long been able to command premium prices. Were this not the case, Novartis would not have paid $8.7bn last year to buy AveXis, a small biotech firm, thereby acquiring Zolgensma, a gene therapy for spinal muscular atrophy (SMA). Most people with SMA lack a working copy of a gene, SMN1, which the nerve cells that control the bodys muscles need to survive. Zolgensma uses an empty virus-like particle that recognises nerve cells to deliver working copies of the gene to where it is needed. Priced at $2.1m per patient, it is the most expensive drug ever brought to market. That dubious accolade might not last long. BioMarin, another biotech firm, is considering charging as much as $3m for a forthcoming gene therapy for haemophilia.

Drug firms say such treatments are economically worthwhile over the lifetime of the patient. Four-fifths of children with the worst form of SMA die before they are four. If, as is hoped, Zolgensma is a lasting cure, then its high cost should be set against a half-century or more of life. About 200 patients had been treated in America by the end of 2019.

But if some treatments for rare diseases may turn a profit, not all will. There are some 6,000 children with SMA in America. There are fewer than ten with Jansens disease. When Dr Nizar asked companies to help develop a treatment for it, she says she was told your disease is not impactful. She wrote down the negative responses to motivate herself: Every day I need to remind myself that this is bullshit.

A world in which markets shrink, drug development gets costlier and new unmet needs are ceaselessly discovered is a long way from the utopian future envisaged by the governments and charities that paid for the sequencing of all those genomes and the establishment of the worlds biobanks. As Peter Bach, director of the Centre for Health Policy and Outcomes, an academic centre in New York, puts it with a degree of understatement: if the world needs to spend as much to develop a drug for 2,000 people as it used to spend developing one for 100,000, the population-level returns from medical research are sharply diminishing.

And it is not as if the costs of drug development have been constant. They have gone up. What Jack Scannell, a consultant and former pharmaceutical analyst at UBS, a bank, has dubbed Erooms lawEroom being Moore, backwardsshows the number of drugs developed for a given amount of R&D spending has fallen inexorably, even as the amount of biological research skyrocketed. Each generation assumes that advances in science will make drugs easier to discover; each generation duly advances science; each generation learns it was wrong.

For evidence, look at the way the arrival of genomics in the 1990s lowered productivity in drug discovery. A paper in Nature Reviews Drug Discovery by Sarah Duggers from Columbia University and colleagues argues that it brought a wealth of new leads that were difficult to prioritise. Spending rose to accommodate this boom; attrition rates for drugs in development subsequently rose because the candidates were not, in general, all that good.

Today, enthused by their big-science experience with the genome and enabled by new tools, biomedical researchers are working on exhaustive studies of all sorts of other omes, including proteomesall the proteins in a cell or body; microbiomesthe non-pathogenic bacteria living in the mouth, gut, skin and such; metabolomessnapshots of all the small molecules being built up and broken down in the body; and connectomes, which list all the links in a nervous system. The patterns they find will doubtless produce new discoveries. But they will not necessarily, in the short term, produce the sort of clear mechanistic understanding which helps create great new drugs. As Dr Scannell puts it: We have treated the diseases with good experimental models. Whats left are diseases where experiments dont replicate people. Data alone canot solve the problem.

Daphne Koller, boss of Insitro, a biotech company based in San Francisco, shares Dr Scannells scepticism about the way drug discovery has been done. A lot of candidate drugs fail, she says, because they aim for targets that are not actually relevant to the biology of the condition involved. Instead researchers make decisions based on accepted rules of thumb, gut instincts or a ridiculous mouse model that has nothing to do with what is actually going on in the relevant human diseaseeven if it makes a mouse look poorly in a similar sort of way.

But she also thinks that is changing. Among the things precision biology has improved over the past five to 10 years have been the scientists own tools. Gene-editing technologies allow genes to be changed in various ways, including letter by letter; single-cell analysis allows the results to be looked at as they unfold. These edited cells may be much more predictive of the effects of drugs than previous surrogates. Organoidsself-organised, three-dimensional tissue cultures grown from human stem cellsoffer simplified but replicable versions of the brain, pancreas, lung and other parts of the body in which to model diseases and their cures.

Insitro is editing changes into stem cellswhich can grow into any other tissueand tracking the tissues they grow into. By measuring differences in the development of very well characterised cells which differ in precisely known ways the company hopes to build more accurate models of disease in living cells. All this work is automated, and carried out on such a large scale that Dr Koller anticipates collecting many petabytes of data before using machine learning to make sense of it. She hopes to create what Dr Scannell complains biology lacks and what drug designers need: predictive models of how genetic changes drive functional changes.

There are also reasons to hope that the new upstream drugsASOs, siRNAs, perhaps even some gene therapiesmight have advantages over todays therapies when it comes to small-batch manufacture. It may also prove possible to streamline much of the testing that such drugs go through. Virus-based gene-therapy vectors and antisense drugs are basically platforms from which to deliver little bits of sequence data. Within some constraints, a platform already approved for carrying one message might be fast-tracked through various safety tests when it carries another.

One more reason for optimism is that drugs developed around a known molecule that marks out a diseasea molecular markerappear to be more successful in trials. The approval process for cancer therapies aimed at the markers of specific mutations is often much shorter now than it used to be. Tagrisso (osimertinib), an incredibly specialised drug, targets a mutation known to occur only in patients already treated for lung cancer with an older drug. Being able to specify the patients who stand to benefit with this degree of accuracy allows trials to be smaller and quicker. Tagrisso was approved less than two years and nine months after the first dose was given to a patient.

With efforts to improve the validity of models of disease and validate drug targets accurately gaining ground, Dr Scannell says he is sympathetic to the proposal that, this time, scientific innovation might improve productivity. Recent years have seen hints that Erooms law is being bent, if not yet broken.

If pharmaceutical companies do not make good on the promise of these new approaches then charities are likely to step in, as they have with various ASO treatments for inherited diseases. And they will not be shackled to business models that see the purpose of medicine as making drugs. The Gates Foundation and Americas National Institutes of Health are investing $200m towards developing treatments based on rewriting genes that could be used to tackle sickle-cell disease and HIVtreatments that have to meet the proviso of being useful in poor-country clinics. Therapies in which cells are taken out of the body, treated in some way and returned might be the basis of a new sort of business, one based around the ability to make small machines that treat individuals by the bedside rather than factories which produce drugs in bulk.

There is room in all this for individuals with vision; there is also room for luck: Dr Nizar has both. Her problem lies in PTH1R, a hormone receptor; her PTH1R gene makes a form of it which is jammed in the on position. This means her cells are constantly doing what they would normally do only if told to by the relevant hormone. A few years ago she learned that a drug which might turn the mutant receptor off (or at least down a bit) had already been characterisedbut had not seemed worth developing.

The rabbit, it is said, outruns the fox because the fox is merely running for its dinner, while the rabbit is running for its life. Dr Nizars incentives outstrip those of drug companies in a similar way. By working with the FDA, the NIH and Massachusetts General Hospital, Dr Nizar helped get a grant to make enough of the drug for toxicology studies. She will take it herself, in the first human trial, in about a years time. After that, if things go well, her childrens pain may finally be eased.

This article appeared in the Technology Quarterly section of the print edition under the headline "Kill or cure?"

Read more here:
New drugs are costly and unmet need is growing - The Economist

Recommendation and review posted by Bethany Smith

DUBLIN, March 13, 2020 /PRNewswire/ -- The "Nitric Oxide - Therapeutics, Markets and Companies" report from Jain PharmaBiotech has been added to ResearchAndMarkets.com's offering.

Share of drugs where NO is involved in the mechanism of action is analyzed in the worldwide pharmaceutical market for 2018 and is projected to 2023 and 2028 as new drugs with NO-based mechanisms are introduced into the market. Various strategies for developing such drugs are discussed.

Several companies have a product or products involving NO and free radicals. The report includes profiles of 35 companies involved in this area of which 9 have a significant interest in NO-based therapeutics. Other players are pharmaceutical and biotechnology companies as well as suppliers of products for NO research. Unfulfilled needs in the development of NO-based therapeutics are identified. Important 18 collaborations in this area are tabulated.

There are numerous publications relevant to NO. Selected 500 references are included in the bibliography. The text is supplemented with 26 tables and 30 figures. It is concluded that the future prospects for NO-based therapies are bright and fit in with biotechnology-based approaches to modern drug discovery and development. It is anticipated that some of these products will help in meeting the unfulfilled needs in human therapeutics.

The report contains information on the following:

The report describes the latest concepts of the role of nitric oxide (NO) in health and disease as a basis for therapeutics and development of new drugs. Major segments of the market for nitric oxide-based drugs are described as well as the companies involved in developing them.

Nitric oxide (NO) can generate free radicals as well as scavenge them. It also functions as a signaling molecule and has an important role in the pathogenesis of several diseases. A major focus is delivery of NO by various technologies. Another approach is modulation of nitric oxide synthase (NOS), which converts L-arginine to NO. NOS can be stimulated as well as inhibited by pharmacological and gene therapy approaches.

Important therapeutic areas for NO-based therapies are inflammatory disorders, cardiovascular diseases, erectile dysfunction, inflammation, pain and neuroprotection. The first therapeutic use of NO was by inhaltion for acute respiratory distress syndrome (ARDS). NO-donors, NO-mimics and NOS modulators are described and compared along with developmental status. NO-related mechanisms of action in existing drugs are identified.

Various pharmacological approaches are described along with their therapeutic relevance. Various approaches are compared using SWOT (Strengths, Weaknesses, Opportunities, Threats) analysis. NO-based therapies are compared with conventional approaches and opportunities for combination with modern biotechnology approaches are described.

For more information about this report visit https://www.researchandmarkets.com/r/m3rdb1

Research and Markets also offers Custom Research services providing focused, comprehensive and tailored research.

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Research and Markets Laura Wood, Senior Manager [emailprotected]

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Nitric Oxide Industry Outlook to 2028 - Pathways, Physiology, Disease, Pharmacology, Therapeutic Applications, Drugs, Therapy Markets, Companies -...

Recommendation and review posted by Bethany Smith

Tim Kelly, PhD

Tim Kelly joins AskBio to lead manufacturing of clinical- and commercial-scale AAV vectors to be used in gene therapy.

RESEARCH TRIANGLE PARK, N.C., March 12, 2020 (GLOBE NEWSWIRE) -- Asklepios BioPharmaceutical, Inc. (AskBio), a leading, clinical-stage adeno-associated virus (AAV) gene therapy company, today announced the appointment of Tim Kelly, PhD, as President of Manufacturing. He will oversee all manufacturing functions at AskBio and its Viralgen affiliate for the production of clinical- and commercial-scale AAV vectors. Prior to joining AskBio, Dr. Kelly was the President and Chief Executive Officer at KBI Biopharma, a contract services organization that provides drug development and biomanufacturing services to pharmaceutical and biotechnology companies globally.

AskBio currently has clinical studies underway in late-onset Pompe disease and congestive heart failure. To meet the growing demand for AAV gene therapies, the company is investing in manufacturing innovation, talent and capacity that will allow it to effectively and efficiently serve patient populations.

Our goal at AskBio is to continue advancing production technology to drive down costs to make gene therapies accessible to all patients who may benefit from treatment. I am delighted that Tim has joined the company to help us shape the future of manufacturing, said Sheila Mikhail, JD, MBA, Chief Executive Officer and co-founder at AskBio. He brings a wealth of experience successfully leading therapeutic development and manufacturing and fostering the entrepreneurial, patient-focused culture that drives us at AskBio.

In January, Viralgen broke ground on a 300,000 square foot commercial facility in San Sebastin, Spain, with production expected to start in the spring of 2022, complementing the clinical-scale production currently carried out at its existing cGMP facility.

AskBios technology is truly transforming human health, and I am incredibly excited to help translate our innovations into reliable delivery of AAV gene therapy products to patients in need, said Dr. Kelly.

More about Tim KellyDr. Kelly has more than 20 years of experience in the development and manufacture of therapeutic proteins. He has overseen biopharmaceutical services for over 320 molecules at all stages of development and commercialization and supported numerous successful FDA and international regulatory inspections throughout his career. He began his tenure at KBI Biopharma in 2005, initially acting as Vice President of Biopharmaceutical Development, where he led the establishment and growth of KBIs analytical development, formulation development and cGMP laboratory services business. He subsequently served as Executive Vice President of Operations with responsibility for KBIs development and manufacturing functions in North Carolina and Colorado before becoming President and Chief Executive Officer. Prior to KBI, he directed the quality control function for Diosynth Biotechnology, where he supported clinical and commercial biopharmaceutical products. Dr. Kelly earned his PhD in molecular genetics and biochemistry from Georgia State University.

About AskBioFounded in 2001, Asklepios BioPharmaceutical, Inc. (AskBio) is a privately held, clinical-stage gene therapy company dedicated to improving the lives of children and adults with genetic disorders. AskBios gene therapy platform includes an industry-leading proprietary cell line manufacturing process called Pro10 and an extensive AAV capsid and promoter library. Based in Research Triangle Park, North Carolina, the company has generated hundreds of proprietary third-generation AAV capsids and promoters, several of which have entered clinical testing. An early innovator in the space, the company holds more than 500 patents in areas such as AAV production and chimeric and self-complementary capsids. AskBio maintains a portfolio of clinical programs across a range of neurodegenerative and neuromuscular indications with a current clinical pipeline that includes therapeutics for Pompe disease, limb-girdle muscular dystrophy 2i/R9 and congestive heart failure, as well as out-licensed clinical indications for hemophilia (Chatham Therapeutics acquired by Takeda) and Duchenne muscular dystrophy (Bamboo Therapeutics acquired by Pfizer). Learn more at https://www.askbio.com or follow us on LinkedIn.

A photo accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/512b3baa-aaff-4a92-8539-152021f4527d

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Tim Kelly Joins AskBio as President of Manufacturing to Lead AAV Vector Production for Gene Therapy - GlobeNewswire

Recommendation and review posted by Bethany Smith

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Gene Therapy Industry Market 2020 |Global Industry Analysis By Trends, Size, Share, Company Overview, Growth And Forecast By 2026| Latest Research...

Recommendation and review posted by Bethany Smith

Familialhypercholesterolemia (FH) is one of the most clinically relevant monogenicdisorders contributing to the development of atherosclerotic cardiovasculardisease (ASCVD). The prevalence of FH was estimated to be 1 in 200 to 1 in 250 individualsin studies in which genetic testing was conducted on large community populationsamples.1 However, the disease often remains undetected and thusuntreated, with only 10% of individuals with FH receiving adequate diagnosisand treatment.2

Notingthe recent accumulation of studies on FH, the authors of a Nature ReviewsCardiology article sought tosummarize the key elements of a model of care for the condition that canbe adapted as new evidence emerges.1 Selected points are highlightedbelow.

Screening and detection. A combination of selective, opportunistic (eg, genetic screening of blood donors), systematic, and universal screening approaches is recommended to improve the detection of FH. Universal screening of children and childparent (reverse) cascade testing is potentially a highly effective method for detecting patients with FH at a young age, before they develop ASCVD32 [and] might be particularly relevant to communities with gene founder effects, noted the review authors. All children with FH should ideally be detected from the age of 5 years or earlier if homozygous FH (hoFH) is suspected.

Diagnosis. In the United States, elevated levels of low-density lipoprotein cholesterol (LDL-C) and a family history of FH are the main phenotypic criteria for FH diagnosis in children. Patients with hoFH, heterozygous FH (heFH), and polygenic hypercholesterolemia may also present with overlapping LDL-C levels, posing a challenge for the development of a standardized diagnostic tool for FH.

Genetic testing. Aninternational expert panel recently endorsed genetic testing in the care ofpatients with FH as it would [allow] a definitive diagnosis, improve[e] riskstratification, address the increasing need for more potent therapies, improve[e]adherence to treatments, and increase[e] the precision and cost- effectivenessof cascade testing.1,3 However, genetic testing remains underuseddue to issues such as cost, low access to genetic counseling, and lack ofclinician knowledge in this area.

Clinical risk assessment.Cumulative lifetime exposure to elevated LDL-C is the key factor driving ASCVDrisk in asymptomatic patients with FH, further underscoring the need for timelydiagnosis and risk stratification. In addition to phenotypic and geneticfactors, imaging of subclinical atherosclerosis, might be the most usefulclinical tool for assessing risk in FH.1 For example, imaging ofcoronary artery calcium can be used to predict coronary events in asymptomaticmiddle-aged patients with FH taking statins, and computed tomography coronaryangiography can be used to assess plaque burden and to intensify therapy.

Care of adults.Emerging evidence continues to support aggressive cholesterol-lowering therapyand lifestyle management in patients with FH from as young as 8 years tomaximally mitigate the cumulative cholesterol burden of risk. The review authorsemphasize the importance of patient-centered care and shared decision making,although health literacy is a challenge that may need to be addressed with somepatients.

Whilethere is insufficient evidence to develop strictly defined LDL-C treatmenttargets, current evidence-based recommendations stipulate that in adultpatients with FH, statin therapy and diet should initially be targeted toachieve a 50% reduction in LDL-cholesterol level and an LDL-cholesterol level<1.8 mmol/l (70 mg/dl) or <2.6 mmol/l (100 mg/dl) for primaryprevention, and <1.4 mmol/l (55 mg/dl) or <1.8 mmol/l (70 mg/dl) forsecondary prevention or for patients at very high risk.1

The addition of ezetimibe is indicated in patients who do not achieve the recommended LDL-C levels with statins alone. The use of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor as a third-line therapy is recommended in those patients or in patients who are intolerant to statins. The addition of a PCSK9 inhibitor in patients with heFH can further reduce LDL-C levels by approximately 60% and lead to recommended treatment targets in more than 80% of patients. However, these agents should not be used during pregnancy, as they cross the placenta and their impact on fetal development has not yet been determined.

Care of children. Extensive evidence supports the treatment of FH starting in childhood, as [m]odest and sustained reductions in LDL- cholesterol levels from early life can have a major effect on reducing mortality associated with ASCVD. Initial therapy is based on lifestyle management in early childhood, with the addition of statins by age 10 years in children with HeFH and upon diagnosis in children with hoFH. Ongoing research is investigating the efficacy and safety of PCSK9 inhibitors in children with heFH or hoFH.4,5

Radical therapies and novel approaches. Lipoprotein apheresis may be required insevere cases of FH, including in pregnant women, and liver transplantationremains the only curative therapy for patients with severe hoFH.

In ongoing studies, an array of novel treatment approaches are being examined, including functional LDL receptor gene transfer therapy in patients with hoFH and targeted RNA-based therapies to lower elevated lipoporotein(a) levels.6-8

Reviewauthors also emphasized the importance of clinical registries, patient supportgroups and networks, and the need for structured research programs that areunderpinned by actionable dissemination and implementation strategies,research skills and training among service providers, and sustainable fundingmodels. They stated that a major challenge is translating new evidence intohealth policy and routine care. Systems approaches for supporting healthorganizations and providers in addressing these gaps in care and serviceprovision are essential.

We spoke with Seth Shay Martin, MD, MHS, associate professor ofmedicine at the Johns Hopkins University School of Medicine in Baltimore,Maryland, and director of the Advanced Lipid Disorders Program of the Ciccarone Center atJohns Hopkins.

Cardiology Advisor: What are examplesof the latest advances in knowledge or practice pertaining to FH?

Dr Martin: A big advance inpractice has been the introduction of PCSK9 inhibitors. When added to statinsand ezetimibe, this class of medications can lower LDL-C by 60% sometimes the reduction can be lower, but inmy experience the effect is commonly approximately 60%. This leads to patientscoming back to clinic really satisfied.

Cardiology Advisor: What is the optimalapproach for the treatment of these patients, and what are some of the toptreatment challenges?

Dr Martin: The optimal approach is to follow the 2018 American Heart Association/American College of Cardiology multi-society guidelines, which recommend a combination approach of lifestyle modification with first-line maximal statin therapy, followed by the addition of ezetimibe and PCSK9 inhibitors. The LDL-C threshold at which additional therapy should be considered is70 mg/dL in high-riskpatients with ASCVD and FH. In patients with isolated FH (termed severe hypercholesterolemia by the guidelines,based on LDL-C levels 190 mg/dL), the LDL-C threshold is 100 mg/dL.

Cardiology Advisor: What are otherrelevant treatment implications for clinicians who treat these patients?

Dr Martin: One of the joys intaking care of a patient with FH is taking care of a family. It is a geneticdisorder with a 50% chance of being passed from parent to child. It is key toperform cascade testing to identify other members of the family; family visitsto the clinic can be beneficial for all.

Cardiology Advisor: What are remaining needs in thisarea?

Dr Martin: There is a great need for increasing awareness and diagnosis rates for FH. This is what our center is working to do as partners of the FH Foundation and as a CASCADE FH Registry site.

References

Go here to read the rest:
Reviewing Evidence on the Screening, Diagnosis, and Care of Familial Hypercholesterolemia - The Cardiology Advisor

Recommendation and review posted by Bethany Smith

BURLINGTON, Mass., March 12, 2020 (GLOBE NEWSWIRE) -- Flexion Therapeutics, Inc. (Nasdaq:FLXN) today reported financial results and recent business highlights for the quarter and the full year ended December 31, 2019.

2019 marked an exciting period of growth for both Flexion and ZILRETTA, said Michael Clayman, M.D., President and Chief Executive Officer. While our full-year sales of $73 million reflect the building market enthusiasm for ZILRETTA, we believe we are still just scratching the surface of its potential. Based on our recent label update, increasing utilization from existing accounts, a growing prescriber base, and most importantly, the strong clinical performance of the product, we have growing confidence that ZILRETTA can become the leading intra-articular therapy for the millions of people who confront osteoarthritis knee pain each year. Furthermore, we continue to investigate ZILRETTAs potential in new indications with our Phase 2 trial in shoulder OA and adhesive capsulitis.

Added Dr. Clayman, ZILRETTA is the engine that will drive our growth in the years ahead and facilitate our goal of becoming the leader in discovering, developing and commercializing new treatments for musculoskeletal conditions. We are making great strides towards this goal as evidenced by the progress of FX201 and FX301, two potentially transformative product candidates.

2019 Financial Highlights

The Company reported a net loss of $149.8 million for full-year 2019 as compared to a net loss of $169.7 million for full-year 2018. Net sales of ZILRETTA were $23.7 million for fourth-quarter 2019 and totaled $73 million for full-year 2019. The cost of sales for full-year 2019 was $10.0 million.

Research and development expenses were $69.6 million and $53.1 million for the years ended December 31, 2019 and 2018, respectively. The increase in research and development expenses year-over-year of $16.5 million was primarily due to an increase in salary and other employee-related costs for additional headcount and stock-based compensation expense and an increase in expenses related to portfolio expansion, ZILRETTA development and other program costs.

Selling, general and administrative expenses were $129.7 million and $121.3 million for the years ended December 31, 2019 and 2018, respectively. Selling expenses were $96.3 million and $87.3 million for the years ended December 31, 2019 and 2018, respectively. The year-over-year increase in selling expenses of $9.0 million was primarily due to salary and other employee-related costs and external costs related to marketing and reimbursement support activities. General and administrative expenses were $33.4 million and $34.0 million for the years ended December 31, 2019 and 2018, respectively, which represents a decrease of $0.6 million year-over-year.

Interest expense was $17.1 million and $15.7 million for the years ended December 31, 2019 and 2018, respectively.

As of December 31, 2019, the Company had approximately $136.7 million in cash, cash equivalents, and marketable securities compared with $258.8 million as of December 31, 2018.

ZILRETTA Commercial MetricsSince the commercial launch of ZILRETTA in November 2017 through December 31, 2019:

Recent News and 2019 Business Highlights

FX201 is a gene therapy product candidate designed to stimulate the production of an anti-inflammatory protein, interleukin-1 receptor antagonist (IL-1Ra), whenever inflammation is present within the joint. Based on preclinical data, the Company believes FX201 holds the potential to provide OA pain relief for a year or more and may slow disease progression.

Conference CallFlexions management will host a conference call today at 4:30 p.m. ET. The dial-in number for the conference call is 855-770-0022 for domestic participants and 908-982-4677 for international participants, with Conference ID #8074875. A live webcast of the conference call can also be accessed through the Investors tab on the Flexion Therapeutics website, and a replay will be available online after the call.

Indication and Select Important Safety Information for ZILRETTA(triamcinolone acetonide extended-release injectable suspension)

Indication:ZILRETTA is indicated as an intra-articular injection for the management of osteoarthritis pain of the knee.

Limitation of Use: The efficacy and safety of repeat administration of ZILRETTA have not been demonstrated.

Contraindication:ZILRETTA is contraindicated in patients who are hypersensitive to triamcinolone acetonide, corticosteroids or any components of the product.

Warnings and Precautions:

Intra-articular Use Only:ZILRETTA has not been evaluated and should not be administered by epidural, intrathecal, intravenous, intraocular, intramuscular, intradermal, or subcutaneous routes. ZILRETTA should not be considered safe for epidural or intrathecal administration.

Adverse Reactions:The most commonly reported adverse reactions (incidence 1%) in clinical studies included sinusitis, cough, and contusions.

Please seeZilrettaLabel.comfor full Prescribing Information.

About ZILRETTAOnOctober 6, 2017, ZILRETTA was approved by the U.S.FDAas the first and only extended-release intra-articular therapy for patients confronting osteoarthritis-related knee pain. ZILRETTA employs proprietary microsphere technology combining triamcinolone acetonide a commonly administered, short-acting corticosteroid with a poly lactic-co-glycolic acid (PLGA) matrix to provide extended pain relief. The pivotal Phase 3 trial on which the approval of ZILRETTA was based showed that ZILRETTA significantly reduced knee pain for 12 weeks, with some people experiencing pain relief through Week 16.

About Osteoarthritis (OA) of the KneeOA, also known as degenerative joint disease, affects more than 30 million adults living in the U.S. and accounts for more than$185 billionin annual expenditures. In 2016, more than 15 million Americans were diagnosed with OA of the knee and the average ageof physician-diagnosed knee OAhas fallen by 16 years, from 72 in the 1990s to 56 in the 2010s. The prevalence of OA is expected to continue to increase as a result of aging, obesity and sports injuries. Each year, approximately five million OA patients receive either an immediate-release corticosteroid or hyaluronic acid intra-articular injection to manage their knee pain.

About FX201FX201 is a locally administered gene therapy product candidate which utilizes a helper-dependent adenovirus (HDAd) vector, designed to stimulate the production of an anti-inflammatory protein, interleukin-1 receptor antagonist (IL-1Ra), whenever inflammation is present within the joint. Inflammation is a known cause of pain, and chronic inflammation is thought to play a major role in the progression of osteoarthritis (OA). By persistently suppressing inflammation, Flexion believes FX201 holds the potential to both reduce OA pain and modify the disease.

About FX301FX301 is a locally administered NaV1.7 inhibitor product candidate, known as funapide formulated for extended release in a thermosensitive hydrogel. The initial development of FX301 is intended to support administration as a peripheral nerve block for control of post-operative pain. Flexion believes FX301 has the potential to provide effective pain relief while preserving motor function and anticipates initiating clinical trials in 2021.

AboutFlexion TherapeuticsFlexion Therapeutics(Nasdaq:FLXN) is a biopharmaceutical company focused on the development and commercialization of novel, local therapies for the treatment of patients with musculoskeletal conditions, beginning with osteoarthritis, the most common form of arthritis. The company's core values are focus, ingenuity, tenacity, transparency and fun. Visitflexiontherapeutics.com.

Forward-Looking Statements This release contains forward-looking statements that are based on the current expectations and beliefs of Flexion. Statements in this press release regarding matters that are not historical facts, including, but not limited to, statements relating to the future of Flexion; our expectations regarding revenues for the year ended December 31, 2020; expected sales growth of ZILRETTA; expected clinical developments and clinical trial timelines; expected increases in the rate of individuals with OA of the knee; and the potential therapeutic and other benefits of ZILRETTA and Flexions product pipeline, are forward looking statements. These forward-looking statements are based on management's expectations and assumptions as of the date of this press release and are subject to numerous risks and uncertainties, which could cause actual results to differ materially from those expressed or implied by such statements. These risks and uncertainties include, without limitation, risk that we may not achieve revenue expectations for 2020; the risk that we may not be able to successfully maintain an effective sales force to commercialize ZILRETTA; competition from alternative therapies; the risk that we may not be able to maintain and enforce our intellectual property, including intellectual property related to ZILRETTA; the risk that ZILRETTA may not be successfully commercialized or adopted; risks regarding our ability to obtain adequate reimbursement from payers for ZILRETTA; risks related to the manufacture and distribution of ZILRETTA, including our reliance on sole sources of supply and distribution; risks related to clinical trials, including potential delays, safety issues or negative results; risks related to key employees, markets, economic conditions, health care reform, prices and reimbursement rates; and other risks and uncertainties described in our filings with theSecurities and Exchange Commission(SEC), including under the heading "Risk Factors" in our Quarterly Report on Form 10-Q for the quarter endedSeptember 30, 2019filed with theSEConNovember 7, 2019and subsequent filings with theSEC. The forward-looking statements in this press release speak only as of the date of this press release, and we undertake no obligation to update or revise any of the statements. We caution investors not to place considerable reliance on the forward-looking statements contained in this press release.

Contact:

Scott YoungVice President, Corporate Communications & Investor RelationsT: 781-305-7194syoung@flexiontherapeutics.com

Julie DownsAssociate Director, Corporate Communications & Investor RelationsT: 781-305-7137jdowns@flexiontherapeutics.com

Excerpt from:
Flexion Therapeutics Reports Fourth-Quarter and Full-Year 2019 Financial Results - GlobeNewswire

Recommendation and review posted by Bethany Smith

Institutes participating in the partnership include the Stanford University School of Medicine, the Fred Hutchinson Cancer Research Center, and Parker Institute for Cancer Immunotherapy.

The Cocoon platform is a closed automated cell therapy manufacturing platform enabling decentralized process development. A transportable cassette that internalizes all of the media, agents, and consumables used in the process is attached inside and the Cocoon closes and begins processing.

Each Cocoon develops therapy for one patient, therefore the technology is patient-scale, and the process can be scaled with many Cocoons, attached on Cocoon trees operating at the same time.

Under the agreement, Lonzas experts will work collaboratively with research teams of the partners to transfer some of their existing cell-based immunotherapies, which are in pre-clinical phase, to the Cocoon bioprocessing system.

Subsequently, the process development will be shared between the partners facilities and Lonzas R&D site in Shady Grove (MD), US.

Once these therapies enter the clinic, whether manufacturing is at the institutes or elsewhere, the Cocoon platform will enable this, Eytan Abraham, head of personalized medicine at Lonza, told us.

Asked about the potential immunotherapies examined, Abraham said that they target a combination of hematological malignancies, solid malignancies, and processes that use non-viral delivery of the gene of interest.

Use of the Cocoon technology can potentially benefit the organizations development projects in several ways, including increased process control, reductions in costs, manpower, time and space requirements, as well as offering superior scalability thereby enabling treatment of larger patient populations.

Further than that, Lonza expects the partnerships to help assess the technology and evaluate the platforms potential to manufacture a range of cell therapies comparable to those manufactured through other processes currently available.

Through these collaborations we are both showcasing the Cocoon advantages and capabilities, but also learning what is needed for decentralized based manufacturing of the next wave of patient scale cell therapies, Abraham told us.

He added that, accordingly, the company will continue to evolve the system to answer these needs, whether they increase cell numbers, improve in-process analytics, integration of additional technologies, such as magnetic cell separation and electroporation, or scaling technologies.

Originally posted here:
Lonza partners with three institutes on Cocoon system - BioPharma-Reporter.com

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Genes may determine what characteristics are passed down from parent to offspring, but each cell expresses these genes differently based on external epigenetic modifications. Epigenetics dont alter the gene sequence (genotype), but they do influence cell behavior and function (phenotype). The study of epigenetics helps us understand how phenotypic changes lead to disease, stem cell differentiation, and essentially, what drives the fate of every cell in the human body.The epigenome is not consistent between cells, or even between cells of the same type. Individual modifications come and go throughout a cells lifetime. Therefore, scientists are faced with the steep challenge as they try to decipher the role of epigenetics in disease and development.[i] Understanding intercellular heterogeneity is key here. The epigenome must be examined at single-cell resolution.

Now, with the advancement of single-cell sequencing methods like the single-cell assay for transposase accessible chromatin (scATAC-seq), researchers have access to sophisticated techniques to map large cell populations, one cell at a time. The resulting epigenomic information provides unprecedented insight into the different cell types that come together to form organs and organ systems, as well as pathogenic modifications associated with disease.

Every single cell has unique epigenomic instructions that guide how it expresses its genes and these instructions are subject to change. A map locating epigenetic modifications in the genome would help scientists understand how epigenetics drives cellular differentiation. But until recently, epigenetic assays mainly focused on select regions of DNA or gave bulk results across an entire sample of cells.[ii] These assays were not designed to detect epigenetic patterns in individual cells.

Single-cell tools like scATAC-seq help us get a grasp on intracellular heterogeneity, differentiate between cell populations and map the role of epigenetics in the larger context of an organism. By building a collection of scATAC-seq data, scientists have begun generating a cell atlas to provide insight into the role of epigenetics during the intricate biological processes that occur throughout the human lifetime.

During ATAC-seq, a hyperactive transposase mutant, Tn5, binds to open chromatin (euchromatin) regions. Wherever Tn5 binds, it cleaves the DNA and attaches sequencing adapters. Then, after PCR amplification, ATAC fragments are sequenced to identify open chromatin regions. ATAC results indicate where nucleosomes are typically positioned in the cell sample and which regions of the genome are open for transcription factors to bind. As such, scientists use ATAC-Seq as a first-pass screening approach to identify changes in chromatin accessibility between samples.

ATAC-seq has many practical applications, but it cant account for the cell-to-cell variability thats often an important aspect of developmental processes and disease. So, researchers developed a new assay in which microfluidic technology is used to isolate individual cells before ATAC-seq.[iv] This assay provides epigenomic information at single cell resolution, earning it the name scATAC-seq.

The key to the scATAC-seq method is that it isolates genomes of individual cells early on to perform a separate ATAC-seq reaction on each individual cell. Then, open regions of the genome are cleaved by the Tn5 transposase, tagged with sequencing adapters and amplified with barcoded cell-identifying primers. Subsequently, the barcoded libraries of ATAC fragments, (each representing an individual cell) are pooled together and sequenced to reveal open chromatin regions of thousands of individual cells.

The first droplet-based iteration of the scATAC-seq method (dscATAC-seq) uses a single cell isolator to encapsulate thousands of individual nuclei in nanoliter-sized droplets for ATAC sequencing. It uses a custom Tn5 transposase to enhance library complexity and signal resolution. Compared to the original microfluidic method, the new workflow is faster and yields greater biological insight with less time and effort spent on sequencing. To demonstrate its power and potential, this technique has been used to conduct an unbiased analysis of the many different cell types and regulatory elements in a mouse brain. [v]

Figure 1:In scATAC-seq, droplet-based technology partitions thousands of whole cells or nuclei into individual nanoliter-sized droplets, enabling researchers to prepare a library of ATAC fragments for sequencing to reveal open chromatin regions. Credit:Bio-Rad Laboratories.

To capture single cell data on a truly massive scale, combinatorial indexing was next introduced into the dscATAC-seq workflow. This new method, called dsciATAC-seq, enables researchers to assess up to 50,000 cells in a single assay. Assaying a large volume of cells is possible because, in dsciATAC-seq, the hyperactive mutant transposase integrates a first set of barcodes as it cleaves open regions of chromatin in each nucleus. Because every cells DNA already carries a barcode, multiple cells can be loaded into a single droplet. Then, as usual, ATAC fragments are amplified with a second set of barcoded primers. After sequencing these fragments, the two sets of barcodes are used to derive epigenomic profiles for tens of thousands of cells.

Putting the dsciATAC-seq method to the test, researchers have studied immune cell clusters from human bone marrow derived cells to illustrate how the chromatin accessibility landscape in these cells changes according to different stimulants at the single cell level.5Although the number of cells that a single scATAC-seq experiment can evaluate has grown dramatically, it will take a continued concerted effort from scientists across many disciplines to create a comprehensive map of the human epigenome, encompassing data from trillions of cells.[vi] Furthermore, to help decode the patterns we find in the human epigenome, it may be valuable to gather information about the epigenomes of animals commonly used as research models. As each of these maps become increasingly detailed, scientists will gain a more thorough understanding of how biological process work and may apply this knowledge towards developing better treatments for complex diseases.

Reference:

[i] Egger, G., et al. Epigenetics in human disease and prospects for epigenetic therapy. Nature, 2004, 429, 457463. doi:10.1038/nature02625[ii] DeAngelis, J. T., Farrington, W. J., & Tollefsbol, T. O. An overview of epigenetic assays. Molecular biotechnology, 2008, 38(2), 179183. doi:10.1007/s12033-007-9010-y[iii] Buenrostro JD, Giresi PG, Zaba LC, Chang HY, Greenleaf WJ. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nature Methods, 2013, 10(12):1213-8. doi: 10.1038/nmeth.2688.[iv] Buenrostro JD, Wu B, Litzenburger UM, Ruff D, Gonzales ML, Snyder MP, Chang HY, Greenleaf WJ. Single-cell chromatin accessibility reveals principles of regulatory variation. Nature, 2015, 523(7561):486-90. doi: 10.1038/nature14590.[v] Lareau, C.A., Duarte, F.M., Chew, J.G. et al. Droplet-based combinatorial indexing for massive-scale single-cell chromatin accessibility. Nature Biotechnology 37, 916924 (2019) doi:10.1038/s41587-019-0147-6.[vi] Bianconi, E., Piovesan, A., Facchin F., Beraudi, A., Casadei. R., Frabetti, F., Vitale, L., Pelleri, M., Tassani. S., Piva, F., Perez-Amodio, S, Strippoli, P. & Canaider, S. An estimation of the number of cells in the human body. Annals of Human Biology, 2013, 40:6, 463-471. doi: 10.3109/03014460.2013.807878.

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Using Single Cells To Get the Whole Picture of the Epigenome - Technology Networks

Recommendation and review posted by Bethany Smith