Congenital Structural Myopathy

COLD SPRING HARBOR, N.Y., Oct. 24, 2024 /PRNewswire/ -- Prostate cancer is a quiet killer. In most men, it's treatable. However, in some cases, it resists all known therapies and turns extremely deadly. A new discovery at Cold Spring Harbor Laboratory (CSHL) points to a potentially groundbreaking solution. CSHL Professor Lloyd Trotman's lab has found that the pro-oxidant supplement menadione slows prostate cancer progression in mice. The supplement is a precursor to vitamin K, commonly found in leafy greens. The story begins more than two decades ago. Continue Reading A new study from Cold Spring Harbor Laboratory Professor Lloyd Trotman and colleagues, published in Science, shows that menadione significantly slows prostate cancer growth in mice and in human-derived cancer cells, as seen here. In 2001, the National Cancer Institute's SELECT trial sought to determine if an antioxidant vitamin E supplement could successfully treat or prevent prostate cancer. The trial involving 35,000 men was planned to last up to 12 years. However, after just three years, participants were told to stop taking their supplements. Not only had vitamin E failed to slow or prevent prostate cancer—more men taking the supplement started to get the disease. Seeing these results, Trotman thought, 'If an antioxidant failed, maybe a pro-oxidant would work.' His new findings in mice show just that. When mice with prostate cancer are given menadione, it messes with the cancer's survival processes. Trotman's team has discovered that menadione kills prostate cancer cells by depleting a lipid called PI(3)P, which works like an ID tag. Without it, the cells stop recycling incoming materials and eventually explode. Trotman explains: "It's like a transport hub, like JFK. If everything that goes in is immediately de-identified, nobody knows where the airplanes should go next. New stuff keeps coming in, and the hub starts to swell. This ultimately leads to the cell bursting." This causes the cancer's progression to slow significantly in mice. Trotman now hopes to see the experiment translated to pilot studies in human prostate cancer patients: "Our target group would be men who get biopsies and have an early form of the disease diagnosed. We wonder if they start to take the supplement, whether we would be able to slow that disease down." Amazingly, Trotman's research suggests menadione may also prove effective against myotubular myopathy, a rare condition that prevents muscle growth in infant boys. Those diagnosed rarely live beyond early childhood. Trotman's lab has found that depleting PI(3)P with menadione can double the lifespan of mice with this condition. If the results hold up in humans, it would mean that men with prostate cancer can enjoy a better quality of life and more time with their families. It could also mean more precious time for children born with an incurable disease. About Cold Spring Harbor Laboratory Founded in 1890, Cold Spring Harbor Laboratory has shaped contemporary biomedical research and education with programs in cancer, neuroscience, plant biology and quantitative biology. Home to eight Nobel Prize winners, the private, not-for-profit Laboratory employs 1,000 people including 600 scientists, students and technicians. For more information, visit SOURCE Cold Spring Harbor Laboratory WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

As it works to rebuild from an earlier gene therapy setback, Astellas is doubling down on the one-and-done modality in a new deal with a London-based startup already in the clinic. Astellas said Tuesday it will pay $30 million upfront and invest $20 million in AviadoBio in exchange for the chance to exclusively develop and commercialize the startup’s AAV-based gene therapy for people with frontotemporal dementia with progranulin mutations, or FTD-GRN. Investigators dosed the first patient with the experimental medicine, codenamed AVB-101, in April. The Phase 1/2 also opened in the US in July. Astellas could deliver up to $2.18 billion in license fees and milestone payments, the companies said. Astellas could develop AVB-101 for FTD-GRN and potentially other indications, the duo added. AviadoBio mentions ALS as another focus area for the startup, according to its website. Patients with FTD, an early form of dementia, can die within three to 13 years after diagnosis, the companies said. Attention, memory, mobility, problem solving and other functions deteriorate in adults with the neurodegenerative disease. AviadoBio’s gene therapy delivers a working copy of the GRN gene into the brain with the goal of halting the disease’s progress. The Astellas investment provides a boost to AviadoBio, which does not appear to have raised another financing round since unveiling an $80 million Series A in December 2021. Leading the upstart is former Novartis Gene Therapies chief business officer Lisa Deschamps. “Together, we can further accelerate delivering this investigational medicine to families around the world who so desperately need treatment options for FTD-GRN and other neurological diseases,” Deschamps said in a press release, noting the company is completing dosing in the first cohort of the ASPIRE-FTD study. The AviadoBio tie-up marks a further bet on gene therapy for Astellas, which ran into a major setback in 2020 and 2021, when four boys died after receiving the company’s gene therapy for a rare neuromuscular disease known as X-linked myotubular myopathy. “People tend to look at the four boys’ deaths. And that’s a very unfortunate and tragic situation,” Astellas CEO Naoki Okamura told Endpoints last month . “On the other hand, there are healthier boys who received [the therapy] and survived for three to five years already. So we believe in the power of gene therapy to really make the difference.” Astellas is working with Kate Therapeutics to improve the safety of the Audentes gene therapy, which is known as resamirigene bilparvovec, or AT132. The drugmaker also has Phase 1-stage gene therapies for Pompe disease (zocaglusagene nuzaparvovec, or AT845) and ASP2016 for cardiomyopathy associated with Friedreich’s ataxia. It also took a write-down in April on a preclinical Friedreich’s ataxia gene therapy known as AT808 from the Audentes buyout. Meanwhile, multiple drugmakers are pulling back from gene therapy R&D, including Pfizer, while a small number of startups have been able to reel in large financing rounds to carry forward their work in the field. The Japanese pharmaceutical company has a gene therapy R&D and manufacturing footprint in the Bay Area; Sanford, NC; and Tsukuba, Japan.

Astellas Pharma is spreading its bets in neurodegenerative disorders, committing $50 million to AviadoBio for the opportunity to license its lead program, an experimental gene therapy for a type of dementia with no FDA-approved drugs. The sum breaks down to a $20 million equity investment and up to $30 million in upfront payments. The deal announced Tuesday grants Astellas an exclusive option to license global rights to the London-based startup’s AVB-101, which is currently in early clinical development as a potential treatment for a certain form of frontotemporal dementia (FTD). FTD is a type of early-onset dementia that leads to rapid decline in functions such as attention control, working memory, and problem solving. It typically causes death within three to 13 years of diagnosis, according to AviadoBio. The company aims to specifically treat this dementia when it is driven by a mutation to the gene that encodes progranulin (PGN), a protein that regulates immune activity in the brain. presented by Health IT Accelerating Claim Processing: Strategies to Shorten the Life of a Claim These strategies and practices can significantly shorten the life cycle of claims, leading to quicker resolutions and improved financial outcomes. By Greenway Health AVB-101 delivers to the central nervous system a functioning copy of the gene that provides instructions for making progranulin. The goal of the one-time treatment is to bring levels of that protein into the range of normal. Administered into the thalamus of the brain, AviadoBio’s therapy is transported to its cellular targets aboard an adeno-associated virus (AAV), an engineered virus widely as a delivery vehicle for genetic medicines. AviadoBio’s science is based on research from King’s College London. The startup emerged from stealth in 2021, backed by $80 million in Series A financing. In preclinical research conducted with progranulin-deficient mice, AviadoBio has reported its experimental FTD-PGN therapy led to expression of progranulin in the brain and a reduction in disease pathology. A Phase 1/2 ascending-dose clinical trial treated its first patient earlier this year. The open-label study has a targeted enrollment of nine participants. There are other efforts underway to try and restore progranulin levels as a way to treat FTD-PGN. Passage Bio’s PBFT02 is a gene therapy intended to boost levels of the key protein in the central nervous system. This program has reached Phase 1/2 testing. Alector is taking a different approach with AL100, an antibody drug designed to bind to a protein that leads to degradation of progranulin. This program has reached Phase 3 testing under a partnership with GSK, which has rights to share in the development and commercialization of this experimental therapy. Gene therapy is one of the areas Astellas has identified for growth, Richard Wilson, the company’s senior vice president for genetic regulation, told MedCity News last year. Within gene therapy, the company is focusing on neuromuscular disorders, central nervous system conditions, and ophthalmology. Astellas’s gene therapy division formed from the 2020 acquisition of Audentes Therapeutics, which brought a pipeline of gene therapies in various stages of development for rare inherited disorders. presented by Health Tech What’s Keeping Healthcare CIOs Up at Night: How to Improve Patient Satisfaction by Handling Calls More Efficiently Health systems have spent billions on portals while investments in modernizing the voice channel — the dominant preference of healthcare consumers — have taken a backseat. By Stephanie Baum Some of the Audentes programs have encountered setbacks. The FDA in 2021 placed a clinical hold on an experimental gene therapy for the enzyme deficiency Pompe disease. That hold was lifted in early 2023. Three gene therapy programs for Duchenne muscular dystrophy were terminated in 2022 based on preclinical data. A gene therapy for the rare neuromuscular disorder X-linked myotubular myopathy was placed under a clinical hold in 2020 following three patient deaths. Though it later was cleared to resume, a fourth patient death in 2021 led to another clinical hold that is still in place. Astellas has prior experience with option deals for gene therapies. Two years ago, Astellas made an equity investment in Taysha Gene Therapies, securing exclusive options to license gene therapies for the rare neurodegenerative disorders giant axonal neuropathy (GAN) and Rett syndrome. Following the report of Phase 1/2 data for the GAN gene therapy last year, Astellas said it would not exercise its option on that program. A key Rett study is ongoing and the option for this program remains open. Astellas has struck other deals to fill its gene therapy pipeline. Last year, the company licensed a preclinical Kate Therapeutics gene therapy in development for X-linked myotubular myopathy. Following that deal, Astellas licensed the rights to use a 4D Molecular Therapeutics AAV vector for ophthalmic diseases. The option agreement with AviadoBio covers the application of AVB-101 to FTD-GRN and other indications. The trigger for the option and the option exercise period were not disclosed. But if Astellas exercises it, AviadoBio could receive up to $2.18 billion in license fees and milestone payments, plus royalties from sales of a commercialized product. “As we complete dosing of the first cohort of patients in our Phase 1/2 ASPIRE-FTD trial of AVB-101, we are excited about the potential of this collaboration to help address the unmet need that exists today in frontotemporal dementia,” AviadoBio CEO Lisa Deschamps said in a prepared statement. “This strategic collaboration will combine our promising gene therapy candidate for FTD-GRN and delivery expertise with Astellas’s global capabilities in development and commercialization of gene therapies.” Public domain image by Flickr user SciTechTrend