A man who received chimeric antigen receptor-T cell therapy shares his firsthand account.

Backer received a diagnosis of diffuse large B-cell lymphoma (DLBCL). It is the most common type of non-Hodgkin lymphoma, which affects nearly 75,000 people mostly men in the United States each year.

Despite multiple rounds of chemotherapy and a stem cell transplant, Backers disease kept relapsing. Then he participated in a clinical trial involving chimeric antigen receptor (CAR)-T cell therapy, which has left him cancer-free for almost three years. With this type of immunotherapy, a patients T cells are removed, altered in a lab and then reinfused in the hope that they will attack cancer cells.

Dr. Frederick L. Locke, a medical oncologist at Moffitt Cancer Center in Tampa, Florida, isco-lead investigator of the pivotal ZUMA-1 trial, which led to the Food and Drug Administration (FDA) approval of the second available CAR-T cell therapy, Yescarta (axicabtagene ciloleucel). During the National Comprehensive Cancer Network 2019 Annual Conference, Locke, Backer and Alix Beaupierre, a transplant nurse coordinator, took a 360-degree look at CAR-T cell therapy.

LIMITED OPTIONSOutcomes in refractory aggressive non-Hodgkin lymphoma are poor, Locke explained. Patientsare often treated upfront with combination chemotherapy, as Backer was. He initially wenton a chemotherapy regimen commonly known as R-CHOP Rituxan (rituximab), cyclophospha- mide, Adriamycin (doxorubicin), Oncovin (vincris- tine) and prednisone. He achieved a complete remission and went back to work.

We can cure up to about 60% of patients with initial chemotherapy, and thats pretty remarkable, Locke said. Unfortunately, 40% of patients either dont respond to chemotherapy or progress.

Backer was among that 40%. He relapsed about a year later and started on a new chemotherapy regimen with a planned autologous stem cell transplant, which would involve removing his own stem cells and later putting them back into his body to help fight the cancer. This treatment plan cures only about 5% of patients, Locke said. Prior to CAR-T cell therapy, more chemotherapy would have been next.

In the United States, two CAR-T therapies are available to patients with certain types of cancer. The first, Kymriah (tisagenlecleucel), was approved in August 2017 for patients up to 25 years old who have acute lymphoblastic leukemia that relapsed or did not go into remission with other treatments. Two months later, the FDA approved Yescarta to treat adult patients with certain types of large B-cell lymphoma who have not responded to or relapsed after at least two other kinds of treatment.In patients with DLBCL, durable responses the length of time that a partial or complete response is observed because of treatment have been seen in 40% of patients who received CAR-T cell therapy. We think we can cure about 15% of people, Locke said. We need these patients referred and referred early.

A NUCLEAR BOMBBacker first read about CAR-T cell therapy on clinicaltrials.gov, an online registry of all clinical trials that anyone can access to see what might be enrolling participants. Im the typeof person who needs a plan A and a plan B, Backer said.I received a plan A, but the plan B in the case of the transplant failing was not encouraging.

He reached out to Moffitt Cancer Center Tampa is not far from where he lived in Orlando, Florida to see if he was eligible. He wasnt. In December 2015, Backer went ahead with the stem cell transplant. A few months later,he again relapsed with growths all over his body butthis made his participation in the ZUMA-1 clinical trial possible. Being a participant in a clinical trial is scary and daunting at the same time, he said. I remember sitting there with the transplant coordinator and they handed me a 27-page consent form, and I could barely read page one. Ijust wanted to sign. I was ready to sign anything right then and there.

Although potentially curative, CAR-T cell therapy is not without risk. Patients can develop two serious side effects. Cytokine release syndrome, caused by a large, rapid release of cytokines (small proteins importantin cell signaling) into the blood from immune cells affected by the immunotherapy, can be life-threatening. Neurological events, such as confusion, tremor and seizures, can also occur.

Despite lengthy discussions with his medical teamat Moffitt and reading the consent form, Backer said,he wasnt fully prepared for the coming side effects and recovery when he went forward with CAR-T therapy in June 2016. Thats when the nuclear bomb set off, he said. Within 12 hours of receiving the infusion, he experienced severe chills, violent shaking and a high fever, and also felt certain he was experiencing side effects that were affecting his brain.

About two days after Backer received the reinfusedT cells, the infectious disease team rushed him in for a CT scan. They found no infection and no signs of the cancer.

For me, it was a miracle treatment, Backer said.

Locke has been following patients enrolled in ZUMA-1 for more than two years and said that half are still alive.

BEING PREPAREDBacker admitted that going in with a full understanding of CAR-T cell therapy would have made the experience dramatically different.

After seeing patients and their loved ones in distress, care providers at Moffitt Cancer Center learned to smooth the process, Beaupierre said. For instance, the 27-page document has been broken down into one-page educational handouts and shorter consent forms. The team also created a flow sheet and that grew to a detailed patient calendar. All CAR-T therapy recipients also now have a dedicated nurse and social worker.

In addition to those resources, Backer said, peer-to-peer support would be helpful.

As CAR-T cell therapy continues to evolve and be explored in the treatment of other cancer types, experts are learning more about how it works and how to improve the process.

For Backer, quality of life has changed a bit. Initially, he received blood and platelet transfusions every two weeks for several months following CAR-T cell therapy. Although he is back to work full time, he runs the risk of being exposed to other diseases and viruses. Its always at the back of my mind, he said. I wear a mask and goggles at work but still get sick.

He spends his free time hiking and fishing and feels blessed to still be alive. It worked out for me, and here we are 33 months into this thing, Backer said.

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Men with breast cancer had a higher mortality rate when compared with women with breast cancer, reported a cohort study recently published in JAMA Oncology. This overall finding aligns with what previous studies have found and highlight the need for better awareness about male breast cancer.

Most people with breast cancer are found to have breast cancer because they have a lump in their breast, and you would think that in men it would be easier to find a lump in the breast, saidJoanne Mortimer, MD, director of City of Hopes Womens Cancer Programs, who was not involved with the study, during an interview with CancerNetwork. Unfortunately, people's suspicion about what's going on in the breast of a man is not the same as a woman.

The study was conducted using the National Cancer Database, and 1,816,733 patients with a breast cancer diagnosis between January 1, 2004, and December 31, 2014 were identified. The totals were 1,800,708 women and 16,025 men.

Men with breast cancer had a significantly worse overall survival (OS) rate (45.8% vs 60.4%; P < .001), 3-year OS rate (86.4% vs 91.7%; P < .001), and 5-year OS rate (77.6% vs 86.4%; P < .001) compared with women with breast cancer, according to the data.

Even when men were diagnosed at the same disease stage as women, their survival outcomes were still inferior. For the 5-year OS rate, men had worse survival than women at stage I (87.8% vs 92.5%; P < .001), stage II (78.9% vs 85.9%; P < .001), stage III (63.3% vs 70.1%; P < .001), and stage IV disease (21.4% vs 25.1%; P = .007).

Several factors were associated with a higher mortality rate among men, including age, clinical characteristics, treatment received, access to care, and race/ethnicity.

However, when all these factors were controlled for, men still have worse survival. The study authors pointed out that this suggests that other factors, particularly additional biological attributes, treatment compliance, and lifestyle factors, should be identified to help in eliminating this disparity.

Clinical and treatment characteristics were the primary factors linked to worse survival, they added.

Clinical characteristics and undertreatments were associated with 63.3% of the excess mortality among male patients, the authors wrote.

The cohort study also revealed that a higher proportion of men were diagnosed with more advanced disease, yet less likely to receive standard treatment. For example, men with hormone receptor-positive breast cancer were less likely to receive adjuvant endocrine therapy compared with women.

These endocrine therapies are very effective at increasing the cure rate of breast cancer, Mortimer. It's unfortunate that these men did not get endocrine therapy as part of their treatment.

In fact, Don Hoffman, a male breast cancer patient who Mortimer helped care for, exemplifies the importance of early detection and proper treatment for men.

Man or woman, early detection is a lifesaver, said Hoffman. He noticed the nipple and areola on his left breast were flatter than usual and had his breast checked by his primary care physician. A mammogram showed a small mass, which was treated. My early detection probably made me a better candidate to live longer.

To Hoffman, one reason why men may be diagnosed later on, when outcomes are worse, is a mans attitude toward seeking medical care. A man's attitude is, Oh, I can tough this out, this is not a big deal, Hoffman said. I think that mindset works against men.

Disclosures:

Wang F, Shu X, Meszoely I. Overall Mortality After Diagnosis of Breast Cancer in Men vs Women. JAMA Oncol. Published online September 19, 2019.

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Men with Breast Cancer Have Worse Mortality, Highlight Need for Better Awareness - Cancer Network

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BARCELONA, Spain Final overall survival (OS) results from the MONARCH 2 and MONALEESA-3 trials show consistent OS benefits with the cyclin-dependent kinase 4/6(CDK4/6) inhibitors abemaciclib (Verzenio, Lilly) and ribociclib (Kisqali, Novartis). The new data establish the foundation for adding these drugs to endocrine therapy in the treatment of patients with hormone receptor positive, human epidermal receptor negative (HR+/HER2-) advanced breast cancer (ABC).

The new results were presented here at the European Society of Medical Oncology (ESMO) 2019 Annual Meeting and were published online September 29 in JAMA Oncology.

The results from MONARCH 2 show that after a median follow-up of approximately 4 years (47.7 months), patients with HR+/HER- ABC lived significantly longer with the combination of abemaciclib and fulvestrant. Median OS was 46.7 months with the combination and 37.3 months with fulvestrant alone (hazard ratio [HR], 0.757; 95% confidence interval [CI], 0.606 0.945; P = .0137).

This is a statistically significant and clinically meaningful improvement in OS, commented first author George Sledge, MD, Stanford University School of Medicine, California.

"The main take-home message from this study and from other similar studies is that CDK4/6 inhibitors significantly prolong the time patients remain in remission and significantly improve overall survival. Therefore, it is very reasonable to think of these as standard-of-care options for patients with metastatic breast cancer," Sledge commented in an ESMO statement.

A similar benefit was seen with the combination of ribociclib and fulvestrant in MONALEESA-3. After a median follow-up of 39.4 months, median OS was not reached with the combination of ribociclib and fulvestrant; it was 40.0 months for patients who received fulvestrant alone (HR, 0.724; 95% CI, 0.568 0.924; P = .00455).

"This is a significant, practice-changing report, in that we are now saying that patients with advanced breast cancer will have an overall survival benefit if they get the CDK4/6 inhibitor ribociclib up front at the time of their recurrence, even if they have not had any prior endocrine therapy at the time of presenting with metastatic disease," commented first author Dennis J. Slamon, MD, PhD, from the David Geffen School of Medicine at the University of California, Los Angeles.

Commenting for ESMO, Matteo Lambertini, MD, of the IRCCS Policlinico San Martino Hospital, University of Genoa, Italy, said, "Uniquely, MONALEESA-3 is the only trial with a CDK4/6 inhibitor to include patients with endocrine-sensitive as well as those with endocrine-resistant disease. This is the first time we have seen improved overall survival with a combination of a CDK4/6 inhibitor plus fulvestrant in first line."

The two trials had different patients populations: MONARCH 2 enrolled premenopausal, perimenopausal, and postmenopausal patients, whereas MONALEESA-3 enrolled only postmenopausal patients. However, a separate study (MONALEESA-7, whih included 1400 patients) reported positive OS results for premenopausal women with HR+/HER2- ABC who received ribociclib and fulvestrant. Slamon said that together, the two MONALESSA trials demonstrated a consistent and meaningful benefit with multiple endocrine therapy partners regardless of menopausal status.

"These are clinically highly meaningful data and are a game changer," commented ESMO expert Nadia Harbeck, MD, of the Breast Center at Ludwig Maximillians University in Munich, Germany. She was speaking at a press briefing at which the results from both trials had been highlighted.

These data will ensure that CDK4/6 inhibitors become the standard of care in treating patients with HR+/HER- ABC and should be used first line because they substantially improve patient outcomes compared with antihormonal treatment alone, Harbeck commented.

"We can never guarantee that patients will come back for second-line therapy. We should give the best drugs first," she said.

Harbeck was optimistic that, in light of the significant OS benefits, costs of these drugs will be reimbursed and that the drugs will be available for those who need it.

Besides abemaciclib and ribociclib, palbociclib (Ibrance, Pfizer) in combination with endocrine-based therapy is also available for use in the first-line and second-line settings of ABC. However, the OS data for this agent were not statistically significant.

At the press conference, questions were raised as to whether the mechanisms of resistance of the three available CDK4/6 inhibitors overlapped, whether they can be given in sequence, and what would dictate the use of one drug over another.

Slamon indicated that although in clinical practice, physicians have been using CDK4/6 inhibitors in sequence, cross-resistance mechanisms should preclude their being used in sequence after resistance develops.

Sledge noted that not enough patients have been followed for long enough and warned that cross-trial comparisons should not be made. In addition, he pointed out that the HRs from progression-free survival (PFS) and OS are impressive and are similar in the studies. "Primary efficacy does not provide any information on the superiority of one drug over the other," he said, but he suggested that the different toxicity profiles may favor one over the other.

Medscape Medical News asked Laura M. Spring, MD, a breast cancer expert from the Massachusetts General Cancer Center in Boston, Massachusetts, for her views on these data and how she integrates CDK4/6 inhibitors in her clinical practice.

Spring explained that CDK4/6 inhibitors are now given in conjunction with endocrine therapy for HR+/HER2- ABC unless there are toxicity concerns for patients. As an example, she indicated that an older patient with only osseous disease who expresses concerns about the side effects of adding a second agent could be given CDK4/6 in the second line after progression occurs with endocrine monotherapy.

The three CDK4/6 inhibitors are similar in efficacy, but they have distinct side effect profiles, she observed. The incidence of neutropenia is higher with ribociclib and palbociclib, whereas diarrhea is a concern with abemaciclib. QTc prolongation is a possible concern with ribociclib, and patients have to be monitored routinely with electrocardiography, Spring noted.

"That is why choosing one over another may be dictated by the other medicines patients are taking as well as their comorbidities," she said. If a patient is taking medication for QTc prolongation, she would be less likely to receive ribociclib, whereas a patient with gastrointestinal problems would be less likely to receive abemaciclib, she said.

All three agents have shown similar PFS benefit in their respective trials. However, the OS benefit now reported with ribociclib and abemaciclib was statistically significant, whereas that reported for palbociclib was not, although there was a trend showing better survival. That data come from the PALOMA-3 trial, which compared the combination of palbociclib and fulvestrant with fulvestrant for patients whose disease had progressed after initial endocrine therapy.

Despite that, patients who received the combination were at a significantly 28% reduced risk for death or progression, Spring observed.

She suggested that the lack of statistical significance was a detail that would most likely be significant only to a purist, owing to the fact that the benefit of these agents as a class is established.

She also noted that OS was the secondary endpoint for all three studies, that PALOMA-3 was not powered to show significance for OS, and that longer follow-up may be needed.

In addition, the patients in PALOMA-3 were heavily pretreated, which is likely to affect clinical outcomes.

Several experts cautioned against making cross-trial comparisons. "The three studies have key eligibility differences, and cross-trial comparisons are not warranted," Spring said.

Spring told Medscape Medical News that, as a standard of care, a physician in the United States can order any of the three agents, depending on the type of insurance coverage a patient carries. The OS data may provide a boost for abemaciclib and ribociclib, she suggested.

Sledge added that at least in the United States, indications overlap for all three CDK4/6 inhibitors and all are already approved in the second-line setting; thus, reimbursement is not likely to change much. "I think it is more likely that the docs will change. When you have an OS advantage, that changes how we feel about a drug," Sledge told Medscape Medical News.

However, Spring pointed out that palbociclib was the first CDK4/6 inhibitor to be approved, and many physicians have a greater "comfort level" with its use.

Ease of dosing and ease of dose reduction are also factors to take into consideration, she added. Abemaciclib is taken twice daily on a continuous dosing schedule, whereas ribociclib and palbociclib are given once daily on a 3-week-on, 1-week-off schedule. Because of its packaging, it is easier to reduce the dose of ribociclib without writing a new prescription, she observed.

"In prescribing CDK4/6 inhibitors to patients, it is important to discuss with them the differences between the agents, which in large measure are minor," Spring said. "But sometimes a small difference makes a big difference to a patient," she added. Some patients may prefer continuous dosing with abemaciclib, whereas others may discount that factor because the drug has to be taken twice daily, she said.

Spring recommends sequencing with another CDK4/6 agent, ideally only in the context of a clinical trial. In MONARCH 2, Sledge reported that subsequent CDK4/6 therapy was provided to 5.8% of patients who experienced disease progression with abemaciclib and fulvestrant.

MONARCH 2 randomized pre-, peri-, and postmenopausal patients with HR+/HER- ABC to receive abemaciclib twice daily on a continuous dosing schedule in addition to fulvestrant (n = 446) or fulvestrant alone (n = 223). These patients were endocrine-therapy resistant but had received no more than one prior endocrine therapy, and they had received no chemotherapy for ABC.

In addition to the new results for OS, reported above, Sledge also presented updated data for PFS (the primary endpoint). Median PFS was 16.9 months with the abemaciclib combination and 9.3 months with fulvestrant. With a hazard ratio (HR) of 0.536, patients who received the abemaciclib combination were at a significantly 44% decreased risk for progression or death (P <0.0001). Three-year PFS was nearly three times higher with the abemaciclib combination: 29.9% vs 10.1% for patients who received fulvestrant.

"At three years, three times as many patients on the combination remain progression free [compared those who received fulvestrant]," Sledge said.

Time to initiation of chemotherapy was an exploratory endpoint of the study. The abemaciclib combination was associated with a 60% delay in the time to initiation of chemotherapy. Median time to initiation was 22.1 months for fulvestrant, vs 50.2 months for the combination (HR: 0.625; P <0.0001).

Sledge reported that there were no additional safety signals and that the safety profile of abemaciclib was consistent with that reported in the primary analysis.

MONALEESA-3 randomly assigned 726 patients with HR+/HER2- ABC to receive oral ribociclib on a 3-weeks-on, 1-week-off dosing schedule in addition to fulvestrant (n = 484) or fulvestrant alone (n = 242). Slamon noted that approximately 50% of patients received these therapies in the first-line setting.

Updated data for the primary endpoint of PFS showed that median PFS was significantly longer for patients who received the combination (20.6 months vs 12.8 months for fulvestrant; HR, 0.587).

In addition to the median OS results reported above, Slamon reported that landmark 3-year OS was 67.0% for patients who received the combination and 58.2% for those who received fulvestrant. In this second prespecified analysis, the P value crossed the prespecified boundary for establishing superior efficacy, Slamon observed. The OS benefits were seen across all subsets of patients, including those distinguished on the basis of site of metastases and line of therapy.

"There was a significant delay in time to first chemotherapy," Slamon observed. The median time to first chemotherapy was not reached in patients who received the combination; it was 29.5 months for those who received fulvestrant.

No new safety signals were observed. Slamon reported on the incidence of grade 3/4 adverse events of special interest with the combination (vs fulvestrant):

Neutropenia: 57.1% vs 0.8%

Hepatobiliary toxicity: 13.7% vs 5.8%

Pulmonary disorders: 0.2% vs 0% (no cases of grade 3/4 pneumonitis or interstitial lung disease were reported)

QTc prolongation: 3.1% vs 1.2% (no episodes of torsades de pointes were observed)

At the meeting, discussant Sibylle Loibl, MD, of the German Breast Group and Goethe University, Frankfurt am Main, Germany, provided some context for the new data.

She noted that each trial had slightly different patient populations. Importantly, patients in MONALEESA-3 were the least heavily pretreated, whereas those in PALOMA-3 were the most heavily pretreated. As the level of pretreatment increased across the trials, the median PFS also decreased, she noted. More heavily pretreated patients will also have a shorter median OS, she noted.

In summarizing the data, Loibl indicated that CDK4/6 inhibitors improved PFS in the first-line and second-line settings of metastatic breast cancer, which translates to an improvement in survival. Improvement in outcomes was seen irrespective of pretreatment, menopausal status, endocrine sensitivity, and site of metastases. A meta-analysis of all the CDK4/6 trials data will likely reveal potential differences in subgroups, she said.

Sledge reports relationships with Eli Lilly, Pfizer, Syndax, Symphogen, Verseau, and Tessa. Slamon reports relationships with Biomarin, Pfizer, Vertex, Lilly, and Novartis. Spring reports relationships with Novartis, Lumicell, Puma, Merck, and Tesaro. Loibl reports relationships with AbbVie, Amgen, AstraZeneca, Celgene, Eirgenix, Novartis, Pfizer, Puma; Roche, Samsung; Seattle Genetics, Teva, Vifor, Daiichi, Cepheid, Myriad, PRIME, and Chugai.

European Society for Medical Oncology (ESMO) 2019 Annual Meeting: Abstracts LBA6_PR (MONARCH 2), LBA7_PR (MONALESSA-3),presented September 29, 2019.

JAMA Oncol. Published online September 29, 2019. Full text

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Now With Survival Benefit, CDK4/6 Inhibitors in Breast Cancer - Medscape

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Vasalgel is inching toward human trials, in part boosted by a $200,000 grant from the Male Contraceptive Initiative (MCI), a private non-profit that focuses on the development of non-hormonal methods.

Heather Vahdat, the executive director of MCI, anticipates that either Vasalgel or another product similar in scope, called Echo-VR, will be the first options supported by the MCI to reach the market some time in 10-plus years.

Vahdat tells Inverse that apart from those two potentials, theres a range of products in the very early stages of development that hold a lot of promise. The goal is to create a future where men have just as many options as women to establish what Vahdat describes as true contraceptive choice.

We are aiming for a contraceptive method mix that benefits everyone, so that partners can consider their future together or individuals can protect themselves, Vahdat explains.

But one concern is that a lack of cash could keep Vasalgel from ever being a real option. Vasalgel is being developed by the Parsemus Foundation a non-profit that takes on products pharmaceutical companies ignore. It collects donations but it usually takes pharmaceutical company-levels of cash to actually get a product to market. The National Institutes of Health is the largest domestic funder of male contraceptive research, while MCI is one of the largest funders globally. Theyve donated just over $2 million to various research programs since 2017, which, while impressive, is still a small amount in the world of pharmaceutical product development.

Back in the 1990s, pharmaceutical research and development for male contraception was an active space. But since then, Long explains, its been virtually abandoned.

The thought is that industry pulled away from male contraceptive development due to concerns that the market was already saturated with female methods, Long says. Moving into the male market, where the risk profile is uncertain, was too risky.

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A joyful heart makes for good health; Despondency dries up the bones. Proverbs 17:22,

Ewings sarcomais a very rare type of canceroustumor that got its name from Dr. James Ewing, the physician who first described it almost exactly a century ago. It affects children through young adults mostly teens and can appear anywhere in the body, but it usually originates in the long bones of the arms and legs, the pelvis or the chest.

The cause of Ewing sarcoma is unknown, and it cant be prevented, but it arises from specific types of cells and it doesnt appear to be inherited. It grows in the bones or the soft tissue around the bones, such as cartilage or the nerves. Significant advanced in treatment, especially at an early stage, have improved survival rates, but when it spreads to distant organs by metastasis, it is very difficult to to treat. After finishing their course of treatment, patients need lifelong monitoring for potential late effects of intense chemotherapy and radiation, as it can return even years after treatment.

The symptoms include pain in the bone or elsewhere, swelling or tenderness near the affected area, unexplained tiredness, unintended weight loss, fragile bones and fever with no known cause.

But there is some hope. A study in mice conducted by researchers at the Weizmann Institute of Science in Rehovot shows that reducing a particular hormone signal keeps the cancer from growing and spreading. They have discovered molecular interactions underlying this kind of tumor and proposed a potential treatment, according to findings they just published in the journal Cell Reports.

Postdoctoral fellow Dr. Swati Srivastava in the laboratory of Prof. Yosef Yarden in the biological regulation department, together with colleagues, conducted research focusing on receptors for steroid hormones called glucocorticoids. These receptors are present in virtually all human cells, conveying hormonal messages related to stress, wakefulness and a host of other important functions.

But sometimes glucocorticoid receptors stimulate malignant growth. They do this by moving to the cell nucleus, where they physically interact and bind with transcription factors molecules that turn genes on or off. The researchers wanted to learn more about the role of these interactions in malignancy.

A highly sensitive protein interaction analysis suitable for living cells revealed previously unknown interactions: Once activated by hormones, glucocorticoid receptors were found to be binding in the cell nucleus to transcription factors of the E-twenty-six (ETS) family, forming together a physical complex. One of the transcription factors in the ETS family is known to drive the development of Ewing sarcoma; its gene fuses abnormally with another gene, creating an oncogene: a cancer-causing gene.

When the study turned up this link between the Ewing sarcoma oncogene and glucocorticoid receptors, the researchers set out to test a hypothesis: that these receptors boost the growth of Ewing sarcoma. A series of studies supplied evidence that this is indeed the case. Physical binding between glucocorticoid receptors and the protein made by this oncogene increased the growth and migration of Ewing sarcoma cells in a lab dish and gave an even stronger boost to the growth and spread of the sarcoma in laboratory mice.

The major medical significance of these findings is that they open the door to a new treatment option for Ewing sarcoma. When the researchers implanted human Ewing sarcoma cells into mice, the tumors grew much more slowly when the mice were treated with metyrapone, a drug that is approved for the treatment of adrenal insufficiency and works by reducing the synthesis of glucocorticoids.

In other experiments, also in mice, another drug, mifepristone which blocks the glucocorticoid receptor and is approved for other clinical applications prevented the metastasis of Ewing sarcoma via a major cancer cell dissemination route, from bone to the lungs. In contrast, when the researchers increased the activity of glucocorticoid receptors, the sarcomas grew and spread much faster.

The researchers also performed a genetic analysis of tumor samples from Ewings sarcoma patients and identified seven genes regulated by the glucocorticoid receptors that were expressed in higher-than-normal levels in patients with particularly lethal tumors.

These genes might serve as a genetic signature enabling a selection of patients for treatment: Those with upregulated signature genes are especially likely to benefit from treatment aimed at neutralizing glucocorticoid receptors. The signature genes may also help predict the course of the disease: Their increased expression may signal a poor prognosis; reduced expression, on the other hand, may signal better chances for survival.

If research in human patients confirms the studys findings, they may offer new hope to youngsters with this malignancy, especially in cases when the sarcoma has metastasized beyond the bone, the researchers said.

Our findings provide the basis for a personalized approach to the treatment of Ewing sarcoma, Srivastava concluded. The fact that the study made use of drugs that have already been approved for other uses should speed up the implementation of this approach.

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Israeli Researcher Discovers a New Way to Block Bone Cancer in Children - Breaking Israel News

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WILMINGTON, Del.--(BUSINESS WIRE)--AstraZeneca and Merck & Co., Inc., Kenilworth, N.J., US (Merck: known as MSD outside the US and Canada) today presented detailed results from the Phase III PROfound trial in 387 men with metastatic castration-resistant prostate cancer (mCRPC) who have a mutation in their homologous recombination repair (HRRm) genes and whose disease had progressed on prior treatment with new hormonal agent (NHA) treatments (e.g. abiraterone or enzalutamide).

The trial was designed to analyze men with HRRm genes in two cohorts: the primary endpoint was in those with mutations in BRCA1/2 or ATM genes and then, if LYNPARZA (olaparib) showed clinical benefit, a formal analysis was performed of the overall trial population of men with HRRm genes (BRCA1/2, ATM, CDK12 and 11 other HRRm genes; key secondary endpoint).

Results showed a statistically significant and clinically meaningful improvement with LYNPARZA in the primary endpoint of radiographic progression-free survival (rPFS), improving the time men with BRCA1/2- or ATM-mutated mCRPC lived without disease progression or death to a median of 7.4 months vs. 3.6 months for those treated with abiraterone or enzalutamide. LYNPARZA reduced the risk of disease progression or death by 66% (equal to a hazard ratio of 0.34) for these men.

The trial also met the key secondary endpoint of rPFS in the overall HRRm population, where LYNPARZA reduced the risk of disease progression or death by 51% (equal to a hazard ratio of 0.49) and improved rPFS to a median of 5.8 months vs. 3.5 months for abiraterone or enzalutamide.

The results were presented during the Presidential Symposium at the 2019 European Society of Medical Oncology (ESMO) congress in Barcelona, Spain (Abstract #LBA12_PR).

Results also showed a trend at this interim analysis time point for improvement in overall survival (OS), another key secondary endpoint, in the two groups. LYNPARZA extended OS to 18.5 months vs. 15.1 months for abiraterone or enzalutamide in men with BRCA1/2- or ATM-mutated tumors, despite that at this interim analysis 81% of patients on NHA crossed over to LYNPARZA at progression. A similar trend in OS was observed at this interim analysis in the overall HRRm population with a median of 17.5 months OS for men treated with LYNPARZA vs. 14.3 months for abiraterone or enzalutamide (analysis at 41% data maturity).

Jos Baselga, Executive Vice President, Oncology R&D, said: Results from PROfound demonstrate that, in addition to providing substantial benefit as a precision medicine for men with metastatic castration-resistant prostate cancer with BRCA-mutated tumors, LYNPARZA is effective beyond just BRCA in tumors with mutations in other genes associated with homologous recombination repair. PROfound validates the concept of PARP sensitivity across multiple genes associated with homologous recombination repair in this disease and marks the first positive Phase III trial using a molecular biomarker to identify men for targeted treatment for metastatic castration-resistant prostate cancer. We are working with global health authorities to bring LYNPARZA to these patients as quickly as possible.

Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, Merck Research Laboratories, said: The results from the Phase III PROfound trial are a testament to Merck and AstraZenecas lasting commitment to patients with cancer. The trial met the primary endpoint in men with metastatic castration-resistant prostate cancer that progressed on prior hormonal therapy, a notoriously difficult-to-treat disease. The benefit seen in patients beyond just those with BRCA mutations underscores the potential value of genomic testing in prostate cancer.

Maha Hussain, one of the principal investigators of the PROfound trial and Deputy Director of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, said: We have seen advances in the treatment over the last 15 years for men with metastatic castration-resistant prostate cancer. However, to date treatments for this state of disease continue to use one size fits all approaches overlooking the genomic make-up of the tumor and how it could inform treatment decisions to better personalize care and impact outcomes. I am thrilled by the PROfound results and LYNPARZAs clinically meaningful benefit which offers the potential of a molecularly targeted treatment for this patient population with advanced disease. I am confident we are now entering a new era of personalized care and precision medicine for metastatic castration-resistant prostate cancer.

Summary of resultsi

Cohort A

(BRCA1/2 or ATM)

Cohort A+B ii

(Overall HRRm)

LYNPARZA

n=162

pcNHA

n=83

LYNPARZA

n=256

pcNHA

n=131

rPFS

Median, months

7.4

3.6

5.8

3.5

% progression-free at 6 months

59.8

22.6

49.7

23.7

% progression-free at 12 months

28.1

9.4

22.1

13.5

Hazard ratio (95% CI)

0.34 (0.25-0.47)

0.49 (0.38-0.63)

p-value

<0.0001

<0.0001

Confirmed ORR

Patients with response (%)

33.3

2.3

21.7

4.5

Odds ratio (95% CI)

20.86 (4.18-379.18)

5.93 (2.01-25.40)

p-value

<0.0001

0.0006 (nominal)

Time to pain progression iii

Median, months

NR

9.92

Hazard ratio (95% CI)

0.44 (0.22-0.91)

p-value

0.0192

OS (interim) iv

Median, months

18.5

15.1

17.5

14.3

Hazard ratio (95% CI)

0.64 (0.43-0.97)

0.67 (0.49-0.93)

p-value

0.0173

0.0063 (nominal)

NR, not reached; ORR, objective response rate; pc, physicians choice i Assessed by blinded independent central review (BICR) ii Cohort B included patients with any 1 of 12 other HRR mutations iii Time to pain progression in Cohort A was a key secondary endpoint included in the formal hierarchy iv Interim analysis was done at 38% (Cohort A) and 41% (Cohort A+B) data maturity; Alpha spend at interim was 0.01; statistical significance not reached

The safety and tolerability profile of LYNPARZA in the PROfound trial was in line with that observed in prior clinical trials. The most common adverse events (AEs) 20% were anemia (47%), nausea (41%), fatigue/asthenia (41%), decreased appetite (30%) and diarrhea (21%). Grade 3 or above AEs were anemia (22%), pulmonary embolism (4%), fatigue/asthenia (3%), vomiting (2%), dyspnea (2%), urinary tract infection (2%), decreased appetite (1%), diarrhea (1%) and back pain (1%). 16% of patients on LYNPARZA discontinued treatment due to AEs.

AstraZeneca and Merck are also exploring additional trials in prostate cancer, including the ongoing Phase III PROpel trial, testing LYNPARZA as a 1st-line therapy in mCRPC, in combination with abiraterone.

LYNPARZA is currently approved for the maintenance treatment of platinum-sensitive relapsed ovarian cancer regardless of BRCA status. It is approved as 1st-line maintenance treatment in BRCAm advanced ovarian cancer following response to platinum-based chemotherapy. It is also approved for germline BRCAm HER2-negative metastatic breast cancer previously treated with chemotherapy. For 1st-line maintenance in advanced ovarian cancer and the metastatic breast cancer setting, physicians should select patients for therapy based on an FDA-approved companion diagnostic. LYNPARZA is not approved in metastatic pancreatic cancer, but an application is currently under regulatory review.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

There are no contraindications for LYNPARZA.

WARNINGS AND PRECAUTIONS

Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): Occurred in <1.5% of patients exposed to LYNPARZA monotherapy, and the majority of events had a fatal outcome. The duration of therapy in patients who developed secondary MDS/AML varied from <6 months to >2 years. All of these patients had previous chemotherapy with platinum agents and/or other DNA-damaging agents, including radiotherapy, and some also had a history of more than one primary malignancy or of bone marrow dysplasia.

Do not start LYNPARZA until patients have recovered from hematological toxicity caused by previous chemotherapy (Grade 1). Monitor complete blood count for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities, interrupt LYNPARZA and monitor blood count weekly until recovery.

If the levels have not recovered to Grade 1 or less after 4 weeks, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. Discontinue LYNPARZA if MDS/AML is confirmed.

Pneumonitis: Occurred in <1% of patients exposed to LYNPARZA, and some cases were fatal. If patients present with new or worsening respiratory symptoms such as dyspnea, cough, and fever, or a radiological abnormality occurs, interrupt LYNPARZA treatment and initiate prompt investigation. Discontinue LYNPARZA if pneumonitis is confirmed and treat patient appropriately.

Embryo-Fetal Toxicity: Based on its mechanism of action and findings in animals, LYNPARZA can cause fetal harm. A pregnancy test is recommended for females of reproductive potential prior to initiating treatment.

Females

Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for 6 months following the last dose.

Males

Advise male patients with female partners of reproductive potential or who are pregnant to use effective contraception during treatment and for 3 months following the last dose of LYNPARZA and to not donate sperm during this time.

ADVERSE REACTIONSFirst-Line Maintenance BRCAm Advanced Ovarian Cancer

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LYNPARZA (olaparib) More Than Doubled the Time Without Radiographic Disease Progression in Patients With BRCA1/2- or ATM-Mutated Metastatic...

Recommendation and review posted by Bethany Smith

Since children were once given radium candy and laudanum, a medication containing opium, that a drug administered to kids could be dangerous is not unprecedented. And now, worry critics, a puberty-blocking medication prescribed for children misidentified as transgender may also be imperiling the young.

As the Christian Postreports, Between 2012 and June 30 of this year, the FDA documented over 40,764 adverse reactionssuffered by patients who took leuprolide acetate (Lupron), which is used as a hormone blocker. More than 25,500 reactions logged from 2014-2019 were considered serious, including 6,370 deaths.

Adverse complications related to its use include breast disorders, malignant neoplasms, and psychiatric and nervous disorders, the Post also informs.

Lupron and other drugs in its class significantly alters the hormone levels in the body and has been documented to contribute to blood clots and other cardiovascular complications, as well as brittle bones and faulty joints, the site continues.

Note, however, that Lupron is said to have at least two legitimate applications (most every drug has its place), the first being halting precocious puberty.

The second application adds perspective to this story. As American Thinker writes, an NBC News piece debunks quite a bit of the Lupron bad press, probably accurately, noting that the drugs in question are often used on terminally ill prostate cancer patients, often as a palliative (such drugs are also sometimes used to treat sex offenders).

Fair enough, but did that reportsay that every last one of those 6,300deaths from users of those drugs was a cancer patient?It didnt, American Thinker continues.So we still dont know.

But heres what we do know: Lupron is being prescribed off-label for use in children who have been diagnosed with gender dysphoria [who claim theyre really the opposite sex] despite the lack of formal FDA approval for that purpose, the Daily Wire tells us.

Something else we can know was related by Michael Laidlaw, a California-based endocrinologist who revealed earlier this year that testosterone is now sometimes given to girls as young as eight years old. Gender dysphoria is not an endocrine condition, but is a psychological one and should, therefore, be treated with proper psychological care, he told the Christian Post in a December 2018 interview.

But it becomes an endocrine condition once you start using puberty blockers and giving cross-sex hormones to kids, he continued.

That gender dysphoria is a psychological issue is not opinion, but what all scientific evidence indicates. While sexual devolutionaries justify their biological interventions (i.e., hormone blockers, surgery) by claiming that a persons sense that hes a member of the opposite sex has a biological basis, this is a pseudo-scientific assertion, as explained in-depth here. Its damaging quackery.

In fact, Laidlaw knows of no psychological condition that is treated by putting hormones out of alignment from their normal levels, the Post also relates.

Moreover, the physician told the National Catholic Register that the drugs in question actually induce a known disease in previously hormonally healthy children.

The site continues, Puberty blockers, he explained, interfere with normal signals between the brain and the sex organs, thereby creating a disease state called hypogonadotropic hypogonadism in youths. Its a serious condition that endocrinologists would normally diagnose and treat because it interferes with development, but in [gender dysphoria] cases theyre inducing this disease state, Laidlaw said.

Additionally, today, medical scenarios such as girls as young as 13 and 14 undergoing double mastectomies and 17-year-old boys with penises of 9-year-olds, developmentally speaking, because of chemical puberty blockers, are now showing up, the Post relates about Laidlaws remarks at a March Heritage Foundation event.

This is all done under the nebulous concept of gender identity, he pointed out, something which no blood test, genetic testing, or brain imaging scans can find, the Post also relates him as saying. Laidlaw lamented that there is no objective test to diagnose this, yet we are giving very harmful therapies on the basis of no objective diagnosis.

He summed up, mincing no words, This whole thing is an experiment on children.

Of course, Laidlaw is hardly alone in sounding this alarm. Think-tank philosopher Ryan T. Anderson pointed out last year that transgenderism is delusion, renowned psychiatrist Dr. Paul McHugh has stated Sex change is biologically impossible, and former transsexual Alan Finch has said that you fundamentally cant change sex.... Transsexualism was invented by psychiatrists, to name just a few joining him.

The kicker is that as many as 88 percent of girls and 98 percent of boys who are gender (sexual-status) confused will naturally outgrow the phase; many transsexuals regret having chosen surgical sexual mutilation; and, according to Dr. McHugh, the suicide rate for those who have chosen it rises to 20 times that of comparable peers.

In reality, sexual-mutilation surgeries are the lobotomies of our time, brought to us by the same psychiatric establishment. Transgender is not a scientific designation, but a political one.

And because so much today is political and not rational is why plastic straws and vaping may be banned, while child-abusing quacks are allowed to commit body-rending malpractice with impunity.

Image: DNY59 via iStock / Getty Images Plus

View original post here:
Puberty Blocking Drug Used on Trans Kids Linked to Thousands of Deaths - The New American

Recommendation and review posted by Bethany Smith

Hey guys, have you heard? Ji Chang Wook is BAAAAACK!

Melting Me Softly, Ji Chang Wooks first post-military drama, tells the story of Ma Dong Chan (Ji Chang Wook) and Go Mi Ran (Won Jin Ah) who volunteer themselves to be frozen for 24 hours as part of a cryogenics experiment-slash-variety show production. However, things go awry when they arent warmed and woken up by the end of the 24 hours, but instead, are woken up 20 years later!

So far, the first two episodes are mostly set in the year 1999 (pre-freeze), and we see the respective social circles of Ma Dong Chan and Go Mi Ran as well as the whys and hows of the cryogenic experiment.

Warning: Spoilers ahead. Proceed with caution!

Ma Dong Chan is an award-winning variety showdirectorwho enjoys taking on challenges and taking risks. His newest fascination is with the study of cryogenics, and he wishes to film the process of freezing and unfreezing humans as part of an experiment conducted by Dr. Hwang (Seo Hyun Chul). Wanting toraise the experiments validity,he volunteers himself to be one of the test subjects while also intending to enlist a female test subject.

Son Hyun Ki (FTISLANDs Lee Hong Ki) suggests Go Mi Ranforthe position. He reminds Dong Chan about Mi Rans risk-taking capabilities as shownby her volunteering for whatever far-fetched experiment Dong Chan was concocting for his variety show Infinite Experiment Paradise. He agrees that she would be a good candidate, but alas, Mi Rans fearlessness stops short ofallowing herself to be frozen.

Dong Chan and Hyun Ki doggedly pursue Mi Ran in hopes to convince her to join them, and they find her hanging around the riverbank with her friends. Also at the riverbank? Mi Rans boyfriend, Hwang Byung Shim (B1A4s Baro), who is on a pedal-boat date. With another girl. That ends as spectacularly as you would imagine it to, and all parties involved end up at the police station for questioning. While Dong Chan doesnt get an opportunity to persuade Mi Ran, he does get a front row seat toher spit-fire personality.

When you have one mate too many.

When Dong Chan does eventually meet Mi Ran, she remains adamant in her refusal. That is, until he mentions that cryonics has reported healing abilities, and they couldbe playing a part in changing how treatments and medicine work in the future.This makes her think of her younger brother, Nam Tae, who has adevelopmental disability, and is finally motivated to join the experiment.

The day of the experiment finally arrives, and Dong Chan and Mi Ran are frozen along with four other undisclosed test subjects. They set the clock for 24 hours, and Hyun Ki and his crew film the whole process for their variety show.

Things go as expected until about two hours left on the clock, whenDr. Hwang suddenly says he has to step out for a bit. His assistant is worried as they have to start the unfreezing process soon, butDr. Hwang insists hell be backvery soon. And so the doctor (who is also the only one capable of unfreezing the test subjects by the way) leaves the facility. Long story short, Dr. Hwang ends up in a car chase, and just whenyou breathe a sigh of relief that hes avoided the truck of doom, his car goes kaboom!

And so,with the 24 hours now up and withoutthe doctor to initiate the unfreezing process, things in the facility rapidly go haywire. The assistant locks the camera crew out, and before anyone realizes whats happening, everything in the lab has disappeared, including the capsules holding the test subjects. Hyun Ki and his superior decide to keep this a secret while also bribing Dong Chans girlfriend Na Ha Young (Chae Seo Jin) tokeep her silence with a position as a prime time news anchor.

The respective families only know that Dong Chan and Mi Ran have gone missing but do not know the details surrounding their disappearance. Dong Chans family persistently hands out missing person flyers over the years hoping to hear any news but to no fruition. Mi Rans family, on the other hand, receives a mysterious envelope clueing them in that Mi Ran is actually alive, but they have to stay quiet if they want her to live.

Thats a little over 6 months, if youre wondering.

Fast forward years later, and we arrive in 2019. It turns out that Dr. Hwang somehow survived the accident (looking completely unscathed too) but has been in a coma. He miraculously wakes up and staggers over to inject Dong Chan and Mi Ran with a serum and starts the unfreezing process. The two of them wake up at different times and make their way out into the world (with a fresh set of clothes no less!). After more staggering, Dong Chancollapsesand gets sent to the hospital, whereas Mi Ran manages to go to quite a few places despite her sickly state. It takes a while for reality to set in, but they finally realize that its no longer 1999, and the people around them have, well, aged 20 years.

There are individual elements of the premiere that I really enjoyed: Ji Chang Wook, Mi Rans relationship with her brother, Mi Ran and her two friends, seeing Hong Ki and Baro one last time before their military enlistments, the feel of the the late 90s, Ji Chang WookAnd yet, for me personally, the premiere as a wholedidnt quite sparkle as much as Id hoped it would. I cant quite place my finger on whats off maybe its the over-the-top sequences like Mi Ran suddenly displaying kung fu skills or the whole opera singer-dinner scene, maybe its the supporting characters (everyone around Dong Chan circa-2019 feels loud), maybe its the pacing, or maybe its something else. Whatever it is, something is preventing me from really falling for the drama.

The scenes of Nam Tae missing his sister were heartbreaking. T.T

With the show now in 2019,there are a different batch of actors taking over the roles(now that theyve aged 20 years).How the chemistry will play out is still yet to be seen, but for sure the younger counterparts will be missed (Baro as the narcissistic, Freud-loving ex-boyfriend is hilarious). The chemistry between the older actors remains unknown, and well just have to wait and see how everything plays out.That being said, I can already imagine Shim Hyung Tak as the older-but-just-as-self-involved Hwang Byung Shim, andit already feels amazing!

See you in 2021, boys!

Storyline-wise,there are parts where the writing may make you want to facepalm, such as when the doctorsuddenlyneeds to leave with two hours left on the clock, orthat the medical staff at the hospital all seem rather lost, or that post-freeze Mi Ran still manages to wander all around the city even though she looks like shes about to collapse any minute. However, the threads of mystery are intriguing enough. I definitely want to know who the other four test subjects are (Is it Freddie Mercury?!), and just how did Dr. Hwang survive that explosion with nary a burn mark?!

All in all, Melting Me Softly has the ingredients to make for a great drama, but it may need a bit more heat to get it to just the right temperature.

If youve watched the premiere, what did you think of it? Do you also feel that there is something off, and if so, what do you think it is? Or are you love, love, loving it instead? Andwhere do you think post-freeze Dong Chan and Mi Ran got the clothes from?Let us know in the comments below!

Belinda_C is excited to have Ji Chang Wook back on her screen again! Talk Melting Me Softly andSEVENTEENwith her onTwitter!

Currently watching:Melting Me SoftlyAll-time favorite:Kill Me Heal Me, Defendant,Hotel Del Luna

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First Impressions: Melting Me Softly Has Warmth, Mystery, And Ji Chang Wook - soompi

Recommendation and review posted by Bethany Smith

DUBLIN--(BUSINESS WIRE)--The "Gene Therapy Market (3rd Edition), 2019-2030" report has been added to ResearchAndMarkets.com's offering.

The Gene Therapy Market (3rd Edition), 2019-2030 report features an extensive study of the current market landscape of gene therapies, primarily focusing on gene augmentation-based therapies, oncolytic viral therapies, and genome editing therapies. The study also features an elaborate discussion on the future potential of this evolving market.

Since the approval of the first therapy, Genedicine in 2003, the gene therapy domain has evolved significantly. Specifically, in 2019, three gene therapies, namely Zolgensma (US), Zynteglo (Europe) and Beperminogene Perplasmid (Japan), have received approval / conditional approval, leading to a marked upward surge in the interest in this field.

In fact, the growing popularity can be correlated to the substantial increase (more than 90%) in the number of patents that have been filed/granted in the last three years. Moreover, in the same time period, more than USD 12.5 billion in the capital has been invested by various private and public investors to fund research activities. Presently, there are more than 10 approved gene therapies in the market, while many others are being investigated across various phases of clinical research.

Over time, the efforts of industry stakeholders and clinical researchers have led to the discovery of novel molecular targets, thereby, strengthening the research pipelines of companies involved in the development of gene therapies. Further, several technology developers have designed innovative ways to improve the efficacy and safety of gene therapies and introduced advanced therapy development and vector engineering platforms.

It is also worth mentioning that, in the last 4-5 years, there has been a marked rise in the M&A activity in this domain, including the involvement of several big pharma players as well. The capability of such therapies to target diverse disease indications is considered to be amongst the most prominent growth drivers of this market. Backed by promising clinical results and several therapy candidates in late phases of development, we believe that the overall market is expected to witness tremendous growth in the coming decade.

One of the key objectives of the report was to estimate the existing market size and the future opportunity for gene therapies, for the next decade. Based on multiple parameters, such as target patient population, likely adoption rates, and expected pricing, we have provided informed estimates on the evolution of the market for the period 2019-2030.

The report also features the likely distribution of the current and forecasted opportunity across:

In order to account for future uncertainties and to add robustness to our model, we have provided three market forecast scenarios, namely conservative, base and optimistic scenarios, representing different tracks of the industry's growth.

Amongst other elements, the report features:

Key Topics Covered:

1 Preface

2 Executive Summary

3 Introduction

4 Gene Delivery Vectors

5 Regulatory Landscape And Reimbursement Scenario

6 Competitive Landscape

7 Marketed Gene Therapies

8 Key Commercialization Strategies

9 Late Stage (Phase Ii/Iii And Above) Gene Therapies

10 Emerging Technologies

11 Promising Therapeutics Areas

12 Patent Analysis

13 Mergers And Acquisitions

14 Funding And Investment Analysis

15 Cost Price Analysis

16 Big Pharma Players: Analysis Of Gene Therapy Related Initiatives

17 Market Forecast And Opportunity Analysis

18 Vector Manufacturing

19 Case Study: Gene Therapy Supply Chain

20 Conclusion

21 Interview Transcripts

22 Appendix 1: Tabulated Data

23 Appendix 2: List Of Companies And Organizations

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

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Global Gene Therapy Market, 2019-2030: Current Market Landscape of Gene Augmentation-Based Therapies, Oncolytic Viral Therapies, and Genome Editing...

Recommendation and review posted by Bethany Smith

Gene editing will be tested in UW Medicine labs on kidney organoids tiny, kidney-like structures grown from stem cells as part of a federally funded effort to develop safe, effective genome editing technologies and therapies.

The National Institutes of Health today, Oct. 1, announced the next set of grant awards for the Somatic Cell Genome Editing consortium, created in 2018. Somatic cells make up the bodys tissues and organs, such as the lungs or blood, in contrast to reproductive cells, like fertilized eggs. Alterations made to somatic cell DNA are not passed down to the next generation.

In the latest round of SCGE funding, twenty-four grants, totaling about $89 million over four years, been awarded across the country. They will fund studies to address the promises and challenges of genome editing in the search for new treatment or cures for a number of genetic disorders.

The human genome contains thousands of genes responsible for making proteins. In many inherited disorders, a variation in the DNA code means that an important protein is not made, or is not made correctly. The missing or faulty protein could result in serious health problems. Genetic editing would aim to change the DNA to enable cells to make a sufficient amount of the proper protein.

For one of the new SCGE projects, collaborative research will take place between the University of Washington School of Medicine lab of kidney disease researcher Benjamin Beno Freedman, assistant professor of medicine, Division of Nephrology, and the University of California Berkeley lab of Jennifer Doudna, professor of molecular and cellular biology.

As a group, Freedman and his fellow researchers bring together expertise in kidney organoids, kidney cell biology, and kidney diseases. Their collaborators at UC Berkeley are leaders in the field of genome editing, including CRISPR-Cas9 gene editing technology to cut and paste portions of DNA in living cells.

Freedmans lab at the UW Medicine Institute for Stem Cell and Regenerative Medicine grow stem cell-derived organoids to study how kidney diseases begin and how they might be treated. Human kidney organoids and kidney-on-a-chip technologies (in which some functions of kidneys are simulated with living cells in tiny chambers) are providing useful medical information. For example, researchers have found new molecules that can reduce the signs of disease in these laboratory models.

Human kidney organoid showing podocytes (red) and proximal tubules (green) developed in the Freedman lab

Freedman explains the importance of exploring responsible gene-editing therapies for inherited kidney diseases: Genetic kidney diseases impact more than half a million people in the United States alone. If we can learn to safely repair the mutation that causes the disease, we can offer a way to treat patients that is much more effective than any current intervention.

Freedman emphasizes that dialysis and transplants two of the most common treatments for kidney diseases are expensive and hard on patients. Kidney transplants are in short supply; donor organs become available to less than 20 % of the patients who need them each year.

The shortcomings of dialysis and transplants make gene therapy an appealing area of research because it might get to the root of the problem.

One of the primary aims of the NIH-funded somatic cell genome editing explorations are to reduce the chances that gene editing produces unintended side effects that do more harm than good. In their collaborative project with UCBerkeley, the UW Medicine team will screen different gene therapies for their effects on normal kidney function and for risks of renal cancer or autoimmune disease.

Our hypothesis is that gene editing will cause adverse effects, but that these effects are predictable and controllable, says Freedman. Our goal is to prove this using laboratory models like organoids and kidneys on chips so we know the approach is safe before we ever involve a human patient.

Freedmans lab is in the Division of Nephrology, Department of Medicine, at the UW School of Medicine, and his lab is also part of the Kidney Research Institute, a collaboration between Northwest Kidney Centers and UW Medicine.

Joining Freedman on the UW Medicine research team are Institute for Stem Cell and Regenerative Medicine colleagues Hannele Ruohola-Baker, professor in biochemistry, and Julie Mathieu, assistant professor of comparative medicine, both at the UW School of Medicine.

Ruohola-Baker will investigate how genome-editing therapies affect cell metabolism. Mathieu adds CRISPR expertise to the UW research team. Several faculty members from other departments are also on the team.

How broad are the implications of developing responsible genome-editing methods?

This is a new paradigm for therapy development, says Freedman. Were looking at the kidney. But the liver, heart, and lungs all have similar challenges. Our hope is to create a model for doing this work in human organoids, which are faster and more humane than animal models, and can be more directly compared to human patients.

Genome editing has extraordinary potential to alter the treatment landscape for common and rare diseases, said Christopher P. Austin, director of the National Center for Advancing Translational Sciences and SCGE Program Working Group chair. The field is still in its infancy, and these newly funded projects promise to improve strategies to address a number of challenges, such as how best to deliver the right genes to the correct places in the genome efficiently and effectively. Together, the projects will help advance the translation of genome-editing technologies into patient care.

Nearly 40 million Americans have chronic kidney disease, a family of progressive conditions that can come with widespread health complications, including a higher risk for heart disease. When kidneys fail, the primary interventions, dialysis and kidney transplants, are not cures. These treatments come with significant side effects and a heavy economic burden. Medicare costs average $114 billion a year total for the care of the nations patients with kidney failure. Altogether, kidney disease is the ninth leading cause of death in the United States.

###

Thatcher Heldring of the Institute for Stem Cell and Regenerative Medicine contributed to this news report.

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Genome editing to be tested in kidney organoids - UW Medicine Newsroom

Recommendation and review posted by Bethany Smith

From the NIH Directors Blog by Dr. Francis Collins

Its a race against time when someone suffers a stroke caused by a blockage of a blood vessel supplying the brain. Unless clot-busting treatment is given within a few hours after symptoms appear, vast numbers of the brains neurons die, often leading to paralysis or other disabilities. It would be great to have a way to replace those lost neurons. Thanks to gene therapy, some encouraging strides are now being made.

In a recent study in Molecular Therapy, researchers reported that, in their mouse and rat models of ischemic stroke, gene therapy could actually convert the brains support cells into new, fully functional neurons.1 Even better, after gaining the new neurons, the animals had improved motor and memory skills.

For the team led by Gong Chen, Penn State, University Park, the quest to replace lost neurons in the brain began about a decade ago. While searching for the right approach, Chen noticed other groups had learned to reprogram fibroblasts into stem cells and make replacement neural cells.

As innovative as this work was at the time, it was performed mostly in lab Petri dishes. Chen and his colleagues thought, why not reprogram cells already in the brain?

They turned their attention to the brains billions of supportive glial cells. Unlike neurons, glial cells divide and replicate. They also are known to survive and activate following a brain injury, remaining at the wound and ultimately forming a scar. This same process had also been observed in the brain following many types of injury, including stroke and neurodegenerative conditions such as Alzheimers disease.

To Chens NIH-supported team, it looked like glial cells might be a perfect target for gene therapies to replace lost neurons. As reported about five years ago, the researchers were on the right track.2

The Chen team showed it was possible to reprogram glial cells in the brain into functional neurons. They succeeded using a genetically engineered retrovirus that delivered a single protein called NeuroD1. Its a neural transcription factor that switches genes on and off in neural cells and helps to determine their cell fate. The newly generated neurons were also capable of integrating into brain circuits to repair damaged tissue.

There was one major hitch: the NeuroD1 retroviral vector only reprogrammed actively dividing glial cells. That suggested their strategy likely couldnt generate the large numbers of new cells needed to repair damaged brain tissue following a stroke.

Fast-forward a couple of years, and improved adeno-associated viral vectors (AAV) have emerged as a major alternative to retroviruses for gene therapy applications. This was exactly the breakthrough that the Chen team needed. The AAVs can reprogram glial cells whether they are dividing or not.

In the new study, Chens team, led by post-doc Yu-Chen Chen, put this new gene therapy system to work, and the results are quite remarkable. In a mouse model of ischemic stroke, the researchers showed the treatment could regenerate about a third of the total lost neurons by preferentially targeting reactive, scar-forming glial cells. The conversion of those reactive glial cells into neurons also protected another third of the neurons from injury.

Studies in brain slices showed that the replacement neurons were fully functional and appeared to have made the needed neural connections in the brain. Importantly, their studies also showed that the NeuroD1 gene therapy led to marked improvements in the functional recovery of the mice after a stroke.

In fact, several tests of their ability to make fine movements with their forelimbs showed about a 60% improvement within 20 to 60 days of receiving the NeuroD1 therapy. Together with study collaborator and NIH grantee Gregory Quirk, University of Puerto Rico, San Juan, they went on to show similar improvements in the ability of rats to recover from stroke-related deficits in memory.

While further study is needed, the findings in rodents offer encouraging evidence that treatments to repair the brain after a stroke or other injury may be on the horizon. In the meantime, the best strategy for limiting the number of neurons lost due to stroke is to recognize the signs and get to a well-equipped hospital or call 911 right away if you or a loved one experience them. Those signs include: sudden numbness or weakness of one side of the body; confusion; difficulty speaking, seeing, or walking; and a sudden, severe headache with unknown causes. Getting treatment for this kind of brain attack within fourhours of the onset of symptoms can make all the difference in recovery.

This research was supported in part by NIA grant AG045656.

References:

[1] Chen Y-C, et al. A NeuroD1 AAV-based gene therapy for functional brain repair after ischemic injury through in vivo astrocyte-to-neuron conversion. Molecular Therapy. 2019. Epub Sept. 6.

[2] Guo Z, et al. In vivo direct reprogramming of reactive glial cells into functional neurons after brain injury and in an Alzheimers disease model. Cell Stem Cell. 2014;14(2):188-202. doi: 10.1016/j.stem.2013.12.001.

Excerpt from:
Gene therapy shows promise repairing brain tissue damaged by stroke - National Institute on Aging

Recommendation and review posted by Bethany Smith

For the past five years, there have been more than 400 mergers and acquisitions with companies in the gene therapy, immuno-oncology, microbiome and orphan drugs therapeutic space in North America and that trend is likely to continue, according to a new analysis.

In its Deal-Making Trends in Pharma analysis, GlobalDatas research shows that in North America, the pharmaceutical industry saw twice the number of M&S activity that the European market saw. When compared to the Asian-Pacific (APAC) market, the U.S. market had seven times the number of M&A deals. Europe had three times as many acquisitions than APAC, GlobalData said.

From 2014 to the first half of 2019, there were 2,882 deals that fell within the gene therapy, immuno-oncology, microbiome and orphan drug space. These deals were worth more than $1 trillion, according to GlobalData. During this time frame, the largest deal types were in the immuno-oncology space with 270 deals in 2018 alone, GlobalData said. That represents a growth of 63% since 2014. Gene therapy showed similar growth of 62% with 133 deals in 2018 compared to 82 deals in 2014.

Jesus Cuaron, associate director of Cardiovascular and Metabolic Disease and Gender Health Pharma at GlobalData, said North America is not only the top region for mergers and acquisitions, but also across each therapeutic theme.

Acquisitions revolving around immuno-oncology assets were the most prominent across the three geographic regions, while acquisitions of microbiome therapies remained low across the board. In the APAC region, no acquisitions were made that involved significant microbiome assets, Cuaron said in a statement.

While many of the M&A deals were on the small side, there have been a number of mega-mergers over the past few years. Among those are Takedas $60 billion acquisition of Shire; Bristol-Myers Squibbs $74 billion deal for Celgene; and AbbVies $63 billion plan to acquire Allergan. Other notable deals include Novartis $8 billion deal for gene therapy company AveXis and Roches $4.8 billion bid for Spark Therapeutics. Other mergers and acquisitions over the past few years can be found here.

Pointing to the mega-deals like BMS bid for Celgene, Cuaron said large-value deals are becoming more common, which signals a new strategy in which stakeholders capitalize on the strengths of other companies. These large-value deals are game-changers for the pharmaceutical industry, Cuaron said, and will cause a ripple of activity within the top pharmaceutical companies.

According to its latest analysis, GlobalData said it anticipates the pharmaceutical industry will continue to be attractive for high volumes of deal activity in the future. That prediction, the analyst said, is based on the fact that the pharmaceutical industry has a track record of making deals with companies that focus on highly specialized biologics and other high-value therapies.

Looking at the potential future of M&A activity, Cuaron said companies are looking to boost their pipelines with more innovative assets and technologies. While licensing agreements are less expensive routes for companies to take to gain an asset, Cuaron said acquisitions are more desirable for most companies because those deals allow the acquiring company to gain complete control over the assets of interest. Cuaron noted that pharmaceutical companies that have few revenue drivers or face patent expiration or generic competition, will be the ones to more quickly flex their M&A muscle. For example, AbbVie has significantly benefited from Humira, which last year generated nearly $30 billion in revenue. However, Humira is facing a patent cliff in 2023 and was seeking a transformational move when it made the bid for Botox-maker Allergan.

At the time Allergan struck the deal, AbbVie said: Smaller bolt-on acquisitions provide opportunities for future growth, but also require significant R&D investment amid scientific and clinical uncertainty. This transaction offers immediate compelling financial and strategic value to our shareholders with a much lower risk profile, which echoes what Cuaron said.

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M&A Will Continue to Be a Mainstay for Growth in the Pharma Industry - BioSpace

Recommendation and review posted by Bethany Smith

When Michael Pirovolakis was born eight days before Christmas in 2017, his green eyes glowed bright like two snow globes.

He had 10 fingers, 10 toes and a full head of hair matted to his head. Michael was a cooing, crying, healthy baby boy.

What else could we ask for, said his father, Terry.

Terry, 39, and his wife Georgia, 41, became a family of five, tucked away in a suburb east of Torontos core.

Michael grew like any ordinary infant, his peanut-coloured hair becoming longer and curlier by the day.

But six months into his life, worry arrived.

Terry says he and Georgia looked at photos of Michaels siblings and began to realize he wasnt reaching the same developmental milestones. Michael wasnt using his hands, didnt crawl and hadnt formed words.

That observation led the family down countless hospital hallways, into waiting rooms and handshakes with many experts in white lab coats.

First, pediatricians noticed Michaels smaller head and a floppiness arising from missing muscle tone. Physiotherapy should have solved the problem, but there was no sign of improvement two months later.

Then, specialists at Torontos Sick Kids Hospital suspected Michael may have contracted the Zika virus from his fathers travels in South America and Puerto Rico for work.

It was pretty scary because they told us he might be blind and deaf, Terry said.

It was a false alarm, but the tests didnt stop. A neurologist said although it was nothing to worry about, the white matter that moves neural signals across Michaels brain was underdeveloped.

It was another dead end, but then came genetic testing and when the results arrived this spring, they contained the answer to every question keeping Michaels parents up at night.

April 2 was doomsday, Terry said.

It was the worst day of my life I saw on the doctors face something was wrong, so they sat us down and told us what it was. It was just an acronym, but then we started reading words like paralyzed, quadriplegic, limited brain function. I honestly dont even know how we got home.

We curled up in a ball and cried for a couple of hours.

SPG50

Michael became one of 61 people on the planet and the only child in Canada known to have spastic paraplegia 50, also called SPG50.

Its a rare disease that will leave Michael with a progressive cerebral palsy effect in his limbs while his mind will fail like a Parkinsons patient, according to Terry, all because of a missing protein in the AP4M1 gene, starving his sons brain.

Hes got this double whammy of stuff happening to him right now.

Michael has suffered seizures and as he ages, his muscles will morph from missing tone to having too much, robbing him of his ability to move. His brain, too, will lose function.

Terry and Georgia didnt waste anytime starting to scour the internet for any bit of information about the disease.

They tracked down a child in Boston living with a similar condition.

For two weeks, that family took care of us, Terry said. We took that information and started running.

He started flying around the world to speak with specialists and pharmaceutical companies, while attending conferences to learn how they could beat the race against time.

I asked them all the same question: If this was your kid, what would you do? he said.

If this was your kid, what would you do?

Many of them pointed to gene therapy and researchers from the University of Texas. After Terry begged them to look at Michael, the team of specialists agreed, saying they could create an experimental therapy to try to cure his son but it would cost $3 million.

Weve liquidated everything weve reversed our mortgage and have taken everything out to try to save our kid, Terry said.

Terry also started a GoFundMe campaign for his child, which went viral, raising $695,032 since it was posted at the start of May.

THE $3 MILLION CURE

On top of the money needed for the experimental treatment, Michael also needs daily physical therapy and occupational therapy, but the government cant cover all the sessions.

If the therapy wasnt experimental, theres a chance the government would fund it and if the condition wasnt as rare as it is, there might be more researchers in Canada searching for a cure but the only option is out of the country, creating another barrier for any kind of financial help.

Terry said he tried contacting Ontario Premier Doug Ford and Prime Minister Justin Trudeau, but didnt receive any support.

Canada as a whole needs to come up with something to help parents, he said. There has to be a mechanism for families like us that are desperate, spending their life savings.

As people around the world organize fundraisers, events, yard sales and even lemonade stands to help Michael, Steven Miller, the head of neurology at SickKids, said Terry is one of the parents leading what could be a revolution within labs.

Were seeing a movement now, especially in Canada, where researchers are working with parents to identify what the next steps are in research, Miller said.

As we wait for the new therapies to evolve, its important not to lose sight for what we can do to help kids with diseases for which there is no cure.

Terry said he spends his mornings talking to the media before going to work for the day and coming home to his family in the evening before researching online until 3 a.m.

Almost two years old now, Michael is walking with assistance and still smiling on his own.

And his family isnt quitting.

Email: bhristova@postmedia.com | Twitter:

Continue reading here:
Race against time for family of toddler with ultra-rare disease, whose only chance at life costs $3 million - National Post

Recommendation and review posted by Bethany Smith

MALVERN, Pa, & TIANJIN, China--(BUSINESS WIRE)--Ocugen, Inc., (NASDAQ: OCGN), a clinical stage biopharmaceutical company focused on innovative therapies that address rare and underserved eye diseases, has entered into a strategic partnership with CanSino Biologics (CanSinoBIO)(6185.HK) on Ocugens gene therapy pipeline product candidates for inherited retinal diseases, which are currently in development with Schepens Eye Research Institute of Massachusetts Eye and Ear, an affiliate of Harvard Medical School.

Under this strategic collaboration, CanSinoBIO will provide all CMC development and clinical supplies for the development of OCU400, Ocugens first gene therapy product candidate in its modifier gene therapy platform. CanSinoBIO maintains the option to support commercial manufacturing for Ocugen. The agreement also provides commercialization rights to CanSinoBIO in Greater China.

We believe our modifier gene therapy platform, and OCU400 as its first product candidate, has the potential to treat many inherited retinal diseases with one product, said Shankar Musunuri, Ph.D., MBA, Chairman, CEO and Co-Founder of Ocugen. A reliable manufacturing partnership is critical for gene therapy clinical trials and commercialization. Partnership with CanSinoBIO, with their state-of-the-art facilities and world class team, provides us a clear path to advance our development and manufacturing processes to reach the clinic.

OCU400 has received two different orphan drug designations (ODD) from the U.S. FDA. The first, for the treatment of NR3E3 mutation-associated retinal degeneration and, most recently, for the treatment of CEP290 mutation-associated retinal disease.

We are delighted to partner with Ocugen as they advance their portfolio of AAV-based gene therapies for rare retinal diseases, said Dr. Xuefeng Yu, the Chairman and Chief Executive Officer of CanSinoBIO. Our expertise in viral vector platform technologies, product development and manufacturing capabilities will play critical roles to advance OCU400 to the clinic and ultimately to serve patients in desperate need for retinal disease therapies.

About OCU400

OCU400 is a novel gene therapy with the potential to be broadly effective in restoring retinal integrity and function across a range of genetically diverse inherited degenerative retinal diseases. OCU400 is the first program that Ocugen is advancing based on its novel modifier gene therapy platform, developed by Neena Haider, PhD, Associate Professor of Ophthalmology at Harvard Medical School and Associate Scientist at the Schepens Eye Research Institute of Massachusetts Eye and Ear, from which Ocugen obtained an exclusive worldwide license to develop and commercialize ophthalmology products based on the platform. Consisting of a functional copy of the nuclear hormone receptor (NHR) gene NR2E3, OCU400 is delivered to target cells in the retina using an adeno-associated viral (AAV) vector. As a potent modifier gene, expression of NR2E3 within the retina may help reset retinal homeostasis, stabilizing cells and potentially rescuing photoreceptors from degeneration.

About Ocugen, Inc.

Ocugen, Inc. is a clinical stage biopharmaceutical company focused on discovering, developing and commercializing a pipeline of innovative therapies that address rare and underserved eye diseases. The Company offers a robust and diversified ophthalmology portfolio that includes novel gene therapies, biologics, and small molecules and targets a broad range of high-need retinal and ocular surface diseases. Ocugen is leveraging its groundbreaking modifier gene therapy platform to address genetically diverse inherited retinal disorders and dry AMD, based on nuclear hormone receptor genes NR2E3 (OCU400) and RORA (OCU410), respectively. OCU400 has received two orphan drug designations (ODD) targeting two distinct IRDs. Ocugen is also developing novel biologic therapies for wet-AMD, DME and diabetic retinopathy (OCU200), as well as for retinitis pigmentosa (OCU100). The Companys late-stage Phase 3 trial for patients with ocular graft versus host disease (oGVHD)(OCU300) leverages Ocugens patented OcuNanoE Ocugens ONE Platform technology to enhance the efficacy of topical ophthalmic therapeutics. OCU300 is the first and only therapeutic with ODD for oGVHD, providing certain regulatory and economic benefits. For more information, please visit http://www.ocugen.com.

About CanSino Biologics Inc.

Incorporated in 2009 in Tianjin, China, CanSinoBIO (6185.HK) commits to research, development, production and commercialization of innovative vaccines for China and global public health. It possesses four integrated platform technologies including viral vectors, conjugation, protein design and recombination and formulation. As of today, it has established a robust pipeline of 15 candidate vaccines covering 12 diseases, including a globally innovative Ebola virus disease vaccine approved for emergency use and stockpile in 2017. For more information, please visit http://www.cansinotech.com.

Cautionary Note on Forward-Looking Statements

This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. We may, in some cases, use terms such as predicts, believes, potential, proposed, continue, estimates, anticipates, expects, plans, intends, may, could, might, will, should or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from the Companys current expectations. These and other risks and uncertainties are more fully described in our periodic filings with the Securities and Exchange Commission (the SEC), including the risk factors described in the section entitled Risk Factors in Histogenics Registration Statement on Form S-4 (Reg. No. 333-232147), as amended, filed with the SEC. Any forward-looking statements that the Company makes in this press release speak only as of the date of this press release. The Company assumes no obligation to update forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.

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Ocugen and CanSinoBIO Enter Strategic Partnership for Gene Therapy Co-Development and Manufacturing - Business Wire

Recommendation and review posted by Bethany Smith

By Adam Vaughan

Bloomberg/Getty Images

Boris Johnson has said the UK can become carbon neutral by the middle of the century and beat the sceptics, in his speech to the Conservative party conference.

The prime minister touched repeatedly on climate change, green technology and science in his address, and suggested that nuclear fusion which the Tories promised 200 million in extra funding over the weekend was on the brink of a breakthrough.

They are on the verge of creating commercially viable miniature fusion reactors for sale around the world, he said of the JET fusion research centre at Culham in Oxfordshire.

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Now I know they have been on the verge for some time. It is a pretty spacious kind of verge, he joked, to laughter in the audience. While the UK is considered a world leader in fusion research, its continued role in a multibillion European fusion project in France has been called into question by Brexit.

In response to Johnsons speech, Tom Nicholas at the University of York says: I would say thats definitely a stretch. Culhams best case would be full technology demonstration by the 2040s, he adds, although even that wouldnt be a commercially viable fusion plant.

Johnson said that while people used to suggest that wind and solar power werent fit for the UK, on some days they were now supplying more than half of the countrys electricity needs.

People years ago said wind turbines would not pull the skin off a rice pudding, Johnson said. He didnt mention that the phrase was his own, which he used when he told The Telegraph in 2013 that the UK should back shale gas, not wind power. Solar power has stalled in the UK and onshore wind farms are no longer being built on the mainland because of policy changes brought in by the Conservative government in 2015.

The prime minister also said the UK was leading on low carbon and battery technology, and said the UK would build a gigafactory, a reference to the sort of large-scale battery factory thatTesla has built in the US. The Labour party used its conference last month to promise three such gigafactories. Battery industry figures have told New Scientistthat the UK is an unlikely candidate for such a facility in Europe, with Germany seen as a much more likely location.

Johnson also promised more zero emission buses and better road and rail links, though he notably didnt mention the High Speed 2 rail project, which is under a government-commissioned review.

The prime minister praised UK leadership in science, saying Manchester led on genomics, gene therapy was being used to cure blindness, and the UK was building two spaceports, one in Newquay and one in Sutherland.

More on these topics:

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Boris Johnson jokes about UK being 'on the verge' of nuclear fusion - New Scientist News

Recommendation and review posted by Bethany Smith

MARTINSRIED, Germany--(BUSINESS WIRE)--

CEO Christian Thirion to Present at Cell and Gene Meeting on the Mesa, California

Exhibition Booth at BioJapan and European Biotech and Pharma Partnering Conference, Japan

Exhibition at ESGCT Annual Conference in Conjunction with ABC of AAV, Spain

SIRION Biotech GmbH (SIRION) today announced its participation in major international conferences this October. SIRION, offering the most comprehensive portfolio of custom viral vectors for preclinical and clinical studies, will present at the Cell and Gene Meeting on the Mesa in Carlsbad, California on October 2 4, and exhibit at the European Biotech and Pharma Partnering Conference in Osaka, Japan on October 8, BioJapan in Pacifico Yokohama, Japan on October 9 11, and the ESGCT 27th Annual Congress on October 22 - 25 in Barcelona, Spain.

This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20191001005658/en/

Organized by the Alliance for Regenerative Medicine, the Cell & Gene Meeting on the Mesa is the sectors foremost annual conference gathering industry leaders and decision-makers to bring forward the state-of-the-art research developments to medicines. Dr. Christian Thirion, CEO, will discuss novel therapeutic viral vectors and technology platforms based on lentivirus, adenovirus, and adeno-associated viruses, which expedite gene therapy research and advances drug development, during his company presentation on Wednesday, October 2 at 4:45 p.m. in the Cognate Bioservices Ballroom at the Park Hyatt Aviara Resort in Carlsbad, CA. A live video webcast of all company presentations will be available at: http://www.meetingonthemesa.com/webcast and will also be published on the conference website shortly after the event.

The Osaka European Biotech and Pharma Partnering Conference offers business contacts to industry professionals who are looking for potential partners in the EU and Japan to ensure sustainable business development and growth. BioJapan is Asias premier partnering event for the global biotech industry. SIRION will be exhibiting at both of these meetings, at the Pacifico Yokohama at D-53. Organized by European Society of Gene and Cell Therapy, the ESGCT Annual Congress in Barcelona promotes basic and clinical research in gene therapy, cell therapy and genetic vaccines by facilitating education, the exchange of information and technology, and by serving as a professional adviser to stakeholder communities and regulatory bodies in Europe. SIRION will exhibit at this meeting at the Barcelona INTERNATIONAL Convention Centre at level P2, booth 20 as part of the ABC of AAV, offering everything you need for gene therapy in one place.

About SIRION Biotech GmbH SIRION Biotech founded in 2005 in Martinsried near Munich, Germany with the goal to skyrocket a new generation of viral vector technologies for gene & cell therapy as well as vaccine development. SIRION advances novel therapeutic viral vectors and uses proprietary technology platforms based on lenti-, adeno-, and adeno-associated viruses, to facilitate its partners successes in drug development. SIRIONs LentiBOOSTTM transduction reagent is actively used to enhance, among others, hematopoietic cell transductions in clinical trials. NextGen AAV capsid evolution projects focus on tissue targeting and immune escape of capsids to accelerate a next generation therapeutics for gene therapy companies. For additional information, please visit http://www.sirion-biotech.com.

View source version on businesswire.com: https://www.businesswire.com/news/home/20191001005658/en/

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SIRION Biotech to Participate in Major International Industry Conferences - Yahoo Finance

Recommendation and review posted by Bethany Smith

In an attempt to fulfill the lofty ambitions of the original Human Genome Project, Duke University engineers, scientists and physicians are joining forces in a new initiative to develop the missing technologies needed to understand the tangled genetic webs underpinning many of humanitys most stubborn diseases and unearth new drug targets and gene therapies to fight them.

The complexity of human biology and the big data stemming from it have all but walled off efforts to comprehensively understand the functions of most of the human genome. To scale these walls, the Duke Center for Advanced Genomic Technologies (CAGT) will build upon its facultys long track record of pioneering tools and techniques to probe the human genome, with a particular focus on teasing out the secrets of the so-called dark genomethe vast but largely unexplored territory of non-protein-coding DNA thought to hold the keys to treating common, complex disorders such as cancer and neurological disease.

There is an amazing team of engineers, scientists and clinicians at Duke coalescing around the challenges of studying and manipulating the human genome to treat disease, said Charlie Gersbach, a leader in the development of CRISPR-based technologies who will direct the CAGT. The mission of the CAGT is to build on their strengths, integrate their expertise, and support their entrepreneurial efforts to maximize impact of tackling grand challenges in genomics and epigenomics.

Launched with the support of the Pratt School of Engineering, the Trinity College of Arts and Sciences and the School of Medicine, the CAGT will focus its efforts on five key areas: genome structure and function, gene regulation, epigenomics of disease, genomics of drug response, and genome engineering technologies. Its faculty are already noted for pioneering advances in genomic tools and technologies, including next-generation DNA sequencing, CRISPR-based genome editing, high-throughput assays of genome structure and gene regulation, and single-cell genomics, which together provide a powerful toolkit for exploring these frontiersespecially the dark genome that makes up 98 percent of our shared blueprint.

In a clear sign of their potential, many of the Duke-born technologies developed for this work formed the basis of a Duke biotech startup called Element Genomics, which was acquired in 2018 by UCB, a global pharmaceuticals company with a focus on neurology and immunology.

Researchers know that the dark genome harbors the genetic regulators responsible for more than 90 percent of susceptibility to common diseases, including neurodegenerative, neuropsychiatric, autoimmune, and cardiovascular disorders, as well as predisposition to cancer. However, most studies of human gene function have completely ignored this gigantic piece of the puzzle, even though it is these mysterious genetic sites that represent a tremendous opportunity to attack diseases from a new direction. The lack of attention to the dark genome has historically been due to a lack of technologies for studying this biology.

With a number of world-leading biomedical engineers and scientists, Duke is emerging as a powerhouse in areas spanning gene therapy, stem cell and organoid technologies, microphysiological human tissue systems for drug testing, single-cell analysis tools, and innovative computational methods for analyzing large genomic datasets. A major goal of the center is to develop and integrate these otherwise disparate technologies and disease areas into a novel, concentrated approach to genomic discovery.

This center is unique in that its focused on decoding the dark genome, said Ravi Bellamkonda, Vinik Dean of the Pratt School of Engineering. This is crucial to understanding complex diseases like schizophrenia, cancer and Alzheimers, and Duke is one of the few places with the depth and breadth of expertise to believe such an outrageously ambitious project might just work.

Moreover, such technologies can be applied to any range of diseases or biological questions. Aside from big plans to tackle the dark genome, a few of the centers first projects aim to identify the gene regulatory networks that distinguish healthy versus diseased immune responses; understand how drugs used in oncology, inflammatory diseases, neurology and genetic diseases impact gene regulation in disease states; and define the function of genetic regulatory elements in different cells and environmental contexts. Identifying the right collaborations to answer the right questions at the right time will be an ongoing process within the CAGT and as part of the international genomics research community.

The CAGT is an important part of our strategic plan to unify and elevate recognition of Dukes tremendous expertise in cutting-edge genomic technologies, said Colin Duckett, vice dean for basic sciences in the Duke University School of Medicine. The opportunities created by building around existing successes of our faculty and integrating their efforts with complementary genomics activities through the new Duke Precision Genomics Collaboratory were clear.

The CAGT will leverage and integrate the range of unique expertise in genomic sciences here at Duke, added Svati Shah, associate dean of genomics in the School of Medicine and director of the Duke Precision Genomics Collaboratory. Its a really exciting endeavor, taking a deeper dive into better understanding the human genome and tackling how these poorly understood areas of the genome can help us better understand rare and common diseases.

The CAGT is directed by Gersbach, the Rooney Family Associate Professor of Biomedical Engineering and associate professor in surgery, who has focused on developing CRISPR technologies for both gene therapy and manipulating the web of biomolecules that determines which genes each cell activates and to what degree. This allows researchers to probe the roles of genes, but also provides methods for perturbing the dark genome in its natural context for the first time.

Additional center leadership includes a steering committee with expertise spanning CAGT focus areas:

Many of us have been doing really fun and interesting work that could have a major impact on human health with support from very different sources like the National Institutes of Health, industry and philanthropy, said Gersbach. Coordinating that collaboration through a focused center is a way to amplify and accelerate what grew organically across the Duke schools and departments and drive our efforts toward improving human health.

For more information, visit cagt.pratt.duke.edu.

Read more:
New Duke Center Takes Aim at the Dark Genome - Duke Today

Recommendation and review posted by Bethany Smith

To develop Ocugens orphan drug designated gene therapy candidate in its modifier gene therapy platform

Ocugen, Inc., a UK based clinical stage biopharmaceutical company focused on innovative therapies that address rare and underserved eye diseases, has entered into a strategic partnership with China based CanSino Biologics on Ocugens gene therapy pipeline product candidates for inherited retinal diseases, which are currently in development with Schepens Eye Research Institute of Massachusetts Eye and Ear, an affiliate of Harvard Medical School.

Under this strategic collaboration, CanSinoBIO will provide all CMC development and clinical supplies for the development of OCU400, Ocugens first gene therapy product candidate in its modifier gene therapy platform. CanSinoBIO maintains the option to support commercial manufacturing for Ocugen. The agreement also provides commercialization rights to CanSinoBIO in Greater China.

OCU400 has received two different orphan drug designations (ODD) from the U.S. FDA. The first, for the treatment ofNR3E3mutation-associated retinal degeneration and, most recently, for the treatment ofCEP290mutation-associated retinal disease.

Continue reading here:
CanSino partners with Ocugen to work on gene therapy - BSA bureau

Recommendation and review posted by Bethany Smith

Astellas Pharma Inc. will invest $12.5 million in two innovation incubators operated by LabCentral, a U.S.-based lab facility for next-generation biotech start-ups. Astellas has previously committed more than $1 billion to drive innovation in Massachusetts to accelerate the discovery and development of potential breakthrough therapies in areas of significant unmet need.

"Astellas has a long-standing commitment to the Boston-area life sciences ecosystem, where world-class talent are dedicated to turning innovative science into value for patients," said Kenji Yasukawa, Ph.D., President and CEO, Astellas. "Our presence in the greater Boston area comprises over 200 professionals across several locations driving innovation in regenerative medicine, immuno-oncology, mitochondrial function, genetic regulation and beyond. Accelerating early-stage scientific innovation in areas such as cell and gene therapy is a strategic focus for Astellas, and is superbly aligned with the mission of LabCentral to serve as a launching-pad for cutting-edge biotech and life sciences start-ups."Astellas will invest $12.5 million to become the only pharma/biopharma company among five Founding Sponsors of a new incubator, which will feature a core lab space where companies can easily conductprocess development studies and a non-GMP pilot plant, being developed by LabCentral in Cambridge. The investment provides support to start-up companies and entrepreneurial founders seeking to create scientific innovation in areas of unmet need such as cell and gene therapy. The new incubator is expected to be operational in 2021.Astellas will also invest at least $450,000 over three years to become a Gold Sponsor of LabCentral's existing incubator located at 700 Main Street in Cambridge.By supporting these incubators, Astellas can select, support and access innovation from leading start-ups creating healthcare solutions in its areas of focus.Since 2010, Astellas has invested more than $800 million in, and committed nearly $500 million more to, Massachusetts-based innovation through the acquisitions of Ocata Therapeutics, Inc., Mitobridge, Inc. and Potenza Therapeutics, Inc., as well as the construction of a state-of-the-art headquarters for the Astellas Institute for Regenerative Medicine (AIRM) in Westborough, MA. The new facility, expected to open in 2020, will enable AIRM to accelerate research and development in the field of regenerative medicine and cell therapy.

Read more:
Astellas to Fund Boston-Area Cell and Gene Therapy Start-Up - Contract Pharma

Recommendation and review posted by Bethany Smith

SAN FRANCISCO--(BUSINESS WIRE)--Audentes Therapeutics, Inc. (Nasdaq: BOLD), a leading AAV-based genetic medicines company focused on developing and commercializing innovative products for serious rare neuromuscular diseases, today announced its planned presentations at the 24th International Annual Congress of the World Muscle Society in Copenhagen, Denmark, including new data from ASPIRO, the clinical trial evaluating AT132 in patients with X-linked Myotubular Myopathy. The oral presentation will be given by Dr. James J. Dowling, Hospital for Sick Children, Toronto, Canada, and will be held during the Clinical Trial Highlights 7 session of the conference on Saturday, October 5 beginning at 1:00pm Central European Summer Time (CEST)/7:00am Eastern Time (ET).

Dr. Dowling will present new efficacy and safety data from the ASPIRO Phase 1/2 dose escalation cohorts (10 treated patients and 2 controls). Efficacy analyses will include assessments of ventilator dependence and achievement of developmental motor milestones.

We are excited to share new efficacy and safety data from our ASPIRO study, stated Natalie Holles, President and Chief Operating Officer. The data from these dose escalation cohorts, along with results from our ongoing pivotal expansion cohort, will form the basis of the AT132 BLA submission planned in mid-2020, and MAA submission planned for the second half of 2020.

Audentes is planning several additional presentations during the conference, including a company-sponsored symposium that will provide an in-depth review of XLMTM and the ASPIRO study results. Following are details for each presentation:

Oral Presentation:

ASPIRO Gene Therapy Trial In X-Linked Myotubular Myopathy (XLMTM): Update on Preliminary Safety And Efficacy FindingsSession: Clinical Trial Highlights 7Date and time: Saturday, October 5, 1:00-2:00pm Central European Summer Time (CEST)/7:00am-8:00am Eastern Time (ET)Abstract number: O.39

Poster Presentation:

INCEPTUS Pre-Phase 1, Prospective, Non-Interventional, Natural History Run-in Study to Evaluate Subjects Aged 4 Years and Younger with X-Linked Myotubular Myopathy (XLMTM)Session: Congenital myopathies: centronuclear and othersDate and time: October 2, 2019, 4:45pm - 6:45pm Central European Summer Time (CEST)/10:45am 12:45pm Eastern Time (ET)Abstract number: P.105

Audentes-Sponsored Symposium:

Altering the Treatment Paradigm: Gene Therapy for Neuromuscular DisordersDate and time: Friday, October 4, 1:15pm2:45pm Central European Summer Time (CEST)/7:15am 8:45am (ET)Location: Axelborg Hall

Agenda and Speakers:AAV Gene Therapy for Neuromuscular DisordersBenedikt Schoser, MD (Chair)Friedrich-Baur Institute, Ludwig-Maximilians University, Munich, Germany

Gene Therapy for XLMTM: The ASPIRO Study

The Potential of AAV for Neuromuscular DisordersEdward Conner, MDSenior Vice President and Chief Medical Officer, Audentes Therapeutics, San Francisco, CA, USA

Improvements in XLMTM Muscle Pathology and BiomarkersMichael W Lawlor, MD, PhDDepartment of Pathology and Laboratory Medicine and Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, WI, USA

Achieving Ventilator Independence with AT132 in XLMTMRobert Graham, MDDivision of Critical Care Medicine, Boston Childrens Hospital, Boston, MA, USA

Attaining Motor Developmental Milestones in Children with XLMTMLaurent Servais, MD, PhDMuscular Dystrophy UK Oxford Neuromuscular Centre, Oxford, UK and Lige University, Lige, Belgium

About X-linked Myotubular Myopathy

X-linked Myotubular Myopathy (XLMTM) is a serious, life-threatening, rare neuromuscular disease that is characterized by extreme muscle weakness, respiratory failure, and early death. Mortality rates are estimated to be 50 percent in the first 18 months of life, and for those patients who survive past infancy, there is an estimated additional 25% mortality by the age of 10. XLMTM is caused by mutations in the MTM1 gene that lead to a lack or dysfunction of myotubularin, a protein that is needed for normal development, maturation, and function of skeletal muscle cells. The disease affects approximately 1 in 40,000 to 50,0000 newborn males.

XLMTM places a substantial burden of care on patients, families and the healthcare system, including high rates of healthcare utilization, hospitalization and surgical intervention. More than 80 percent of XLMTM patients require ventilator support, and the majority of patients require a gastrostomy tube for nutritional support. In most patients, normal developmental motor milestones are delayed or never achieved. Currently, only supportive treatment options, such as ventilator use or a feeding tube, are available.

About AT132 for the treatment of XLMTM

Audentes is developing AT132, an AAV8 vector containing a functional copy of the MTM1 gene, for the treatment of X-linked Myotubular Myopathy (XLMTM). AT132 may provide patients with significantly improved outcomes based on the ability of AAV8 to target skeletal muscle and increase myotubularin expression in targeted tissues following a single intravenous administration.

Audentes has reported promising safety, efficacy, and muscle biopsy data from ASPIRO, an ongoing, multicenter, ascending dose clinical study designed to evaluate the safety and efficacy of AT132. The preclinical development of AT132 was conducted in collaboration with Genethon (www.genethon.fr).

AT132 has been granted Regenerative Medicine and Advanced Therapy (RMAT), Rare Pediatric Disease, Fast Track, and Orphan Drug designations by the U.S. Food and Drug Administration (FDA), and Priority Medicines (PRIME) and Orphan Drug designations by the European Medicines Agency (EMA).

About Audentes Therapeutics, Inc.

Audentes Therapeutics (Nasdaq: BOLD) is a leading AAV-based genetic medicines company focused on developing and commercializing innovative products for serious rare neuromuscular diseases. We are leveraging our AAV gene therapy technology platform and proprietary manufacturing expertise to develop programs across three modalities: gene replacement, vectorized exon skipping, and vectorized RNA knockdown. Our product candidates are showing promising therapeutic profiles in clinical and preclinical studies across a range of neuromuscular diseases. Audentes is a focused, experienced and passionate team driven by the goal of improving the lives of patients.

For more information regarding Audentes, please visit http://www.audentestx.com.

Forward Looking Statements

This press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, the timing and nature of the ASPIRO pivotal expansion and the ASPIRO clinical data results and the timing and nature of regulatory filings for AT132. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. Although the company believes that the expectations reflected in such forward-looking statements are reasonable, the company cannot guarantee future events, results, actions, levels of activity, performance or achievements, and the timing and results of biotechnology development and potential regulatory approval is inherently uncertain. Forward-looking statements are subject to risks and uncertainties that may cause the company's actual activities or results to differ significantly from those expressed in any forward-looking statement, including risks and uncertainties related to the company's ability to advance its product candidates and obtain regulatory approval of and ultimately commercialize its product candidates, the timing and results of preclinical and clinical trials, the company's ability to fund development activities and achieve development goals, the company's ability to protect intellectual property and other risks and uncertainties described under the heading "Risk Factors" in documents the company files from time to time with the Securities and Exchange Commission. These forward-looking statements speak only as of the date of this press release, and the company undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date hereof.

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Audentes Announces Upcoming Presentations at the 24th International Annual Congress of the World Muscle Society, Including New Data From ASPIRO, the...

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A study has revealed that using DNA-like molecules to repair gene mutations in models could act as a successful therapy for patients.

Researchers have used a promising new therapeutic to treat Duchenne muscular dystrophy (DMD) in human muscle cells and mice models. According to the researchers, their treatment could aid as many as 47 percent of patients with the condition.

The study, conducted by the University of Alberta, US, investigated whether using a group of DNA-like molecules would result in regrowth of a protein called dystrophin, which supports muscle strength. Patients with DMD often severely lack this protein.

In muscle, if there is no dystrophin there is no support of muscle membrane and the muscle cells will become easily damaged or destroyed, said Toshifumi Yokota, a professor of medical genetics at the university. Our DNA-like molecules restore the production of dystrophin so it can support the muscle cell membrane.

The team used a mix of DNA-like molecules, known as antisense oligonucleotides, to act in the manner of a stitch to repair a specific gene mutation in patients.

Our treatment produces a shorter dystrophin protein than the drug being used now. This shorter protein is associated with extremely mild symptoms in some of the muscular dystrophy patients. Some have almost no symptoms at all, explained Yokota.

The researchers are now working to reduce the number of DNA-like molecules in the mixture to reduce both cost and regulatory hurdles moving forward. They hope to progress the work to a clinical trial in the future.

The results were published in Molecular Therapy.

See more here:
Researchers find DNA therapy could treat patients with DMD - Drug Target Review

Recommendation and review posted by Bethany Smith

I favor running analogies even the name of this column pays tribute to the sport. But Im not the first patient advocate to evoke that ancient sport of quicker-than-average terrestrial locomotion. After all, we are racing to treatments because time is critical.

But in the fight against a rare condition like Batten disease, success involves much more than speed. You may be fast, but have you studied the course? Do you know its twists and turns? Do you have a team and support crew, or are you competing alone? Are you ready to take on unexpected obstacles?

Do you have what it takes?

Therapy development isnt for the faint of heart, but patients can and absolutely do make an impact on potentially life-saving treatments and the science and regulatory issues involved. Last month, I joined my mom, Taylors Tale President Sharon King, and Steven Gray, PhD, associate professor at University of Texas Southwestern Medical Center, onstage at the Global Genes RARE Patient Advocacy Summit to discuss that topic.

If you didnt make it to San Diego for the summit this year, I hope you had a chance to tune in to the livestream. If you didnt, or if youd like a recap, following are nine things that we shared about pushing promising work toward the finish line.

Like a marathon, the race to find treatments and cures isnt easy. Few people see the long hours in the lab or the thousands of experiments that dont produce a single breakthrough or correct answer. Miracles happen in science, but results come with a lot of hard work and some luck.

If you want to see a treatment for you or someone you love, you have to accept that it wont be easy. This race is hard. Youll feel winded. Youll get injured. Youll crave water stops. Youll get passed by someone running faster than you. Youll pass someone who doesnt want it as much as you do.

In his new book Chasing My Cure, my friend, David Fajgenbaum, writes, Fear disintegrates. Doubt disorganizes. Hope clears the way, pushes out the horizon, and gives us space to build structures.

Heres what I think David meant by that:

Being invincible in hope means having the courage and the will to take action. You cant trust and wait. You cant assume that someone else will swoop in to save the day. Thats not what hope means.

Instead, you have to look inward. You have to take an active role in transforming hope into reality. Thats hope in action.

Thats how you change the world.

Never doubt that a small group of thoughtful, committed citizens can change the world. Indeed, it is the only thing that ever has. Margaret Mead

***

Note: Batten Disease News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Batten Disease News or its parent company, BioNews Services, and are intended to spark discussion about issues pertaining to Batten disease.

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9 Things We Should Know About the Race to New Treatments - Batten Disease News

Recommendation and review posted by Bethany Smith

STONY BROOK, N.Y.--(BUSINESS WIRE)--LineaRx, Inc., the majority-owned subsidiary of Applied DNA Sciences, Inc. (NASDAQ: APDN) focused on next-generation biotherapeutics, announced today that its invasive Circulating Tumor Cells (iCTCs) platform demonstrated superior correlation over Prostate Specific Antigen (PSA) in an ongoing Phase II trial in recurrent prostate cancer. Most notably, the concentration of rare iCTCs identified per milliliter of whole blood correlated more directly with disease status than did the levels of PSA. These iCTCs were captured and identified utilizing LineaRxs technology platform recently acquired from Vitatex Inc.

LineaRxs collaborator Tyme Technologies, Inc. (NASDAQ: TYME), reported yesterday results of this recently completed Phase II trial using SM-88 to treat recurrent prostate cancer at the Congress of the European Society of Medical Oncology (ESMO), one of the preeminent meetings for highlighting new cancer therapies and diagnostics. The study updated the safety and antitumor effects of SM-88 in men with non-castrate non-metastatic prostate cancer. Antitumor effects were assessed by post-therapy changes in PSA and the number of iCTCs. Results showed that patients treated with this oral non-hormonal therapy maintained metastases-free survival without testosterone deprivation or typical hormonal therapy side effects.

Dr. Wen-Tien Chen, Principal Investigator of CTC Programs at LineaRx stated: This use of iCTC quantification for providing earlier and more accurate identification of prostate cancer shows the importance of running trials using the iCTC functional capture and identification system from LineaRx. Published studies have shown that the concentration of iCTCs in blood correlates with disease status across other hard tumors, including metastatic sarcoma, pancreatic, ovarian, breast, lung and colorectal cancers. We believe our proprietary platform can help diagnose these difficult cancers earlier and with superior predictive capability.

The current reported SM-88 Phase II study examines iCTCs in prostate cancer for what we believe is the first time in a clinical trial. While PSA has historically been the recognized biomarker for prostate cancer, many studies over the last 20 years have shown it is an inadequate biomarker, since it may become elevated in patients with no apparent disease, or less serious pathology than cancer. Intensive efforts have been directed towards alternative prostate cancer biomarkers, particularly those that can predict disease aggressiveness and help to drive better treatment decisions. However, biomarker research has centered on disease diagnostics, rather than prognosis and prediction, which could work toward disease preventionan important focus moving forward.

The authors concluded: "Reductions in iCTC number may be a more informative indicator of benefit than changes in PSA. Dr. Chen added, New prostate cancer biomarkers should be targeted to addressing unmet clinical needs in prostate cancer management, including indicators for disease with low PSA values (<10ng/mL), prognostic markers to distinguish indolent from aggressive disease, and biomarkers for metastatic cancer.

LineaRxs iCTC technology is unique in that it isolates iCTCs on a functional basis (the invasion of a model tissue for the extracellular matrix, or the tissue between cells in an organ) and allows the cells to be cultured for deeper genomic analysis. iCTCs are a model for metastasis, since the tumor cells have left the primary tumor and entered the circulation. The LineaRx platform may serve as a standalone device or as a front-end to increase the sensitivity of approved diagnostics.

iCTCs have the potential for metastasis, and may be very useful in the diagnosis of cancer, even before tumors may be imaged, said Dr. James Hayward, CEO of LineaRx. The present study is exciting because we believe it shows that iCTCs may be used to accurately follow therapy success in this very prevalent cancer while also providing new tools for cell and gene therapy design and production.

About Tyme Technologies, Inc

Tyme Technologies, Inc., is an emerging biotechnology company developing cancer therapeutics that are intended to be broadly effective across tumor types and have low toxicity profiles. Unlike targeted therapies that attempt to regulate specific mutations within cancer, Tyme Technologies, Inc.s therapeutic approach is designed to take advantage of a cancer cells innate metabolic weaknesses to compromise its defenses, leading to cell death through oxidative stress and exposure to the bodys natural immune system. For more information, visit http://www.tymeinc.com. Follow Tyme Technologies, Inc. on social media: @tyme_Inc, LinkedIn, Instagram, Facebook and YouTube.

About LineaRx

LineaRx seeks to commercialize the biotherapeutic value of Applied DNAs deep expertise and experience in the design, manufacture and chemical modification of DNA by large scale polymerase chain reaction (PCR). Linear DNA is a form of DNA distinct from the circular form of DNA most commonly produced in plasmids and grown in bacteria. Plasmids are extrachromosomal DNA found in bacteria and are associated with the genes for antibiotic resistance which are often exchanged between bacteria and consequentially, are seen by many to embody a serious threat to global health. In addition, many nucleic acid-based therapies also rely on viral vectors for efficient transfection and expression of plasmid DNA. These viral vectors carry additional nontrivial risks and are extremely time consuming and expensive to manufacture. Go to http://www.adnas.com for more information on LineaRx and to learn more about how Applied DNA makes life real and safe. LineaRx is a majority-owned Applied DNA Sciences, Inc. (Nasdaq: APDN) company.

About Applied DNA Sciences

Applied DNA is a provider of molecular technologies that enable supply chain security, anti-counterfeiting and anti-theft technology, product genotyping and pre-clinical nucleic acid-based therapeutic drug candidates.

Applied DNA makes life real and safe by providing innovative, molecular-based technology solutions and services that can help protect products, brands, entire supply chains, and intellectual property of companies, governments and consumers from theft, counterfeiting, fraud and diversion.

Visit adnas.com for more information. Follow us on Twitter and LinkedIn. Join our mailing list.

Common stock listed on NASDAQ under the symbol APDN, and warrants are listed under the symbol APDNW.

Forward-Looking Statements

The statements made by Applied DNA in this press release may be forward-looking in nature within the meaning of the Private Securities Litigation Act of 1995. Forward-looking statements describe Applied DNAs future plans, projections, strategies and expectations, and are based on assumptions and involve a number of risks and uncertainties, many of which are beyond the control of Applied DNA. Actual results could differ materially from those projected due to the risk that the acquisition will not be successfully integrated with LineaRx or that the potential benefits of the acquisition will not be realized, the Companys history of net losses, limited financial resources, limited market acceptance , the uncertainties inherent in research and development, future clinical data and analysis, including whether any of Applied DNAs product candidates will advance further in the preclinical research or clinical trial process, including receiving clearance from the U.S. Food and Drug Administration or equivalent foreign regulatory agencies to conduct clinical trials and whether and when, if at all, they will receive final approval from the U.S. FDA or equivalent foreign regulatory agencies, uncertainties relating to its ability to maintain its NASDAQ listing in light of delisting notices received and various other factors detailed from time to time in Applied DNAs SEC reports and filings, including our Annual Report on Form 10-K filed on December 18, 2018, as amended, and our subsequent quarterly reports on Form 10-Q filed on February 7, 2019,May 9, 2019 and August 13, 2019, and other reports we file with the SEC, which are available at http://www.sec.gov. Applied DNA undertakes no obligation to update publicly any forward-looking statements to reflect new information, events or circumstances after the date hereof to reflect the occurrence of unanticipated events, unless otherwise required by law.

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LineaRx's iCTC Platform for Isolation of Circulating Tumor Cells Shows Superior Correlation over PSA as a Biomarker in Prostate Cancer Trial -...

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The Universities of Bristol and Nottingham will share over 500k to lead a consortium of experts on research projects into bioengineered blood and soft tissue regeneration, respectively. The research could not only save lives, but could also improve the quality of lives of injured personnel.

The funding is awarded at Phase 2 of the Defence and Security Accelerator (DASA) Regenerative Medicine themed competition which is facilitated and managed by the Defence Science and Technology Laboratory (Dstl) on behalf of the MOD, in partnership with the Academic Department of Military Surgery and Trauma (ADMST).

Dealing with damage caused by blast or ballistic trauma, which may involve significant blood loss and multiple complex wounds, is a challenge for even the most sophisticated medical facility. Yet to do this in the austere and remote environments within which the military operate further complicates the delivery of medical care.

Approaches in tissue engineering and regenerative medicine hold great promise for the treatment of injured service personnel and the new Defence regenerative medicine research strategy is focussed on delivering such advanced therapies in a way suitable for use in the field early after injury.

The 500k funding will enable the University of Bristol to continue its research to engineer a multi-compatible blood type, with an improved storage profile, that could be used to treat military personnel regardless of their blood type. This could transform the logistics of transporting and storing blood supplies on the front line. In the longer term, first responders like paramedics could also benefit from the portability of a blood supply that is suitable for all.

The University of Nottingham will continue to research a novel approach to preserve and regenerate soft tissue after blast and ballistic trauma through transient gene therapy. Preserving living tissue after injury is critically important, and will significantly improve quality of life.

Dave Henson, co-founder of the CASEVAC club, a support network for individuals that were severely wounded in combat, said:

Understanding that saving a life on the battlefield without due consideration for the future quality of that life is nonsensical. Significant progress has been made in the medical arena throughout the duration of recent conflicts. The development of technologies such as were seeing in this latest of the DASA competition, with the reduction in burden associated with blood supplies, and the immediate improvement of wound management techniques, provides strong assurances that the functional outcome from battlefield trauma will continue to improve.

Dr Abi Spear, Technical Lead for the regenerative medicine project at Dstl said:

Im delighted that the Universities of Bristol and Nottingham have won this Phase 2 competition. Their work represents innovative, discovery science thats high risk but with potentially huge clinical benefit.

Dr Adam Staines, Themed Competition Lead, DASA:

We are pleased that this competition has harnessed cutting edge bio-medical research that seeks to make a real difference on the front line and could also have positive implications for the civilian market in future too.

The Dstl regenerative medicine research strategy looks to support research in four areas, as defined by an evidence-based scoping study, through a variety of activities, including funding and collaboration. If you would like more information on the project as a whole please email DSTLRegenDefenceAccelerator@dstl.gov.uk.

Read more here:
Defence investment set to transform recovery from combat trauma - GOV.UK

Recommendation and review posted by Bethany Smith

People with spinal muscular atrophy (SMA) type 1 may have an increased risk of impaired kidney function, a small study suggests.

The studys findings highlight the need to further evaluate non-muscular conditions associated with SMA type 1 and to identify co-adjuvant therapies to manage them.

The research was published in the article, Impaired kidney structure and function in spinal muscular atrophy, in the journal Neurology Genetics.

SMA is caused by mutations in theSMN1 gene, which leads to reduced production of the SMN protein. While motor nerve cells are those most vulnerable to SMN deficiency, decreased levels of this protein occur throughout the body, which may contribute to the development of the disease.

With new therapies to treat all types of SMA, including type 1 (the most common and one of the most severe types), patients are living longer, and thus the overall impact of SMN deficiency beyond motor function needs to be evaluated, scientists say.

In addition, an increased risk of renal toxicity is listed on the insert for Spinraza, the first therapy approved by the U.S. Food and Drug Administration to treat SMA, and similar therapies have been associated with acute tubular injury, the researchers wrote.

With this in mind, they evaluated whether kidney function was impaired in 13 children with SMA type 1 who died due to SMA complications.

Analysis of blood data showed that most of the children had values outside of the expected range for several molecules associated with kidney function, including creatinine and cystatin C. Most of them also had potentially harmful aggregates, called granular casts and amorphous crystals, and high levels of amino acids (the building blocks of proteins) in their urine, which are all linked with kidney damage.

Molecular and morphological analyses of kidney tissues of 12 patients as well as age- and sex-matched children without SMA showed that two-thirds of the SMA patients had several abnormalities highly associated with kidney disease.

Kidney tissues of children with SMA type 1 showed varying degrees of tubular damage, with scarring and abnormal calcium deposits, and significant changes in the levels of genes associated with kidney toxicity or kidney cystic disease.

Also, they had low levels of CaSR and CALB1 (proteins involved in the maintenance of their calcium balance, thus preventing accumulation of calcium deposits) and high levels of IGFBP1 and IGFBP3 which has been associated with kidney damage and dysfunction compared with the non-SMA children.

The researchers noted all these features were consistent with kidney dysfunction more specifically kidney tubular dysfunction which strongly suggests that most of the children with SMA type 1 had impaired kidney function before death.

Therefore, the study recommends that physicians consider this increased risk of impaired kidney function when treating their patients with SMA type 1.

The researchers also noted that since these patients are now living longer due to recently approved treatments, kidney disease may become a significant comorbidity, and future research should focus on identifying therapies to manage kidney dysfunction.

Future studies will be important to determine whether impaired kidney function is a primary consequence of reduced SMN protein, a secondary consequence of muscle atrophy and bone disease, or more likely a combination of both, the researchers said.

Total Posts: 85

Ana holds a PhD in Immunology from the University of Lisbon and worked as a postdoctoral researcher at Instituto de Medicina Molecular (iMM) in Lisbon, Portugal. She graduated with a BSc in Genetics from the University of Newcastle and received a Masters in Biomolecular Archaeology from the University of Manchester, England. After leaving the lab to pursue a career in Science Communication, she served as the Director of Science Communication at iMM.

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SMA Type 1 Kids May be at Higher Risk of Kidney Dysfunction, Study Says - SMA News Today

Recommendation and review posted by Bethany Smith