Greenstone Biosciences’ Post

Groundbreaking Angiogenic Gene Therapy Shows Promise In Refractory Angina: EXACT Phase 2 Trial Refractory angina, a debilitating condition characterized by persistent chest pain despite optimal medical therapy, poses significant challenges for patients and clinicians alike. However, a beacon of hope shines through the latest advancements in medical science. The results of the EXACT Phase 2 Trial, investigating the efficacy of angiogenic gene therapy in refractory angina patients, have been unveiled, heralding a potential breakthrough in treatment. According to the trial, gene therapy for therapeutic angiogenesis showed promise for patients with angina who had already exhausted their options for medical therapy and coronary revascularization. The findings were published online in Circulation: Cardiovascular Interventions. #CirculationCardiovascularInterventions #angiogenesis #coronaryarterydisease #genetictherapy #vascularendothelialgrowthfactorA #refractoryangina

Interested in Gene Therapy? Check out our review article, "Gene Therapy for Cardiac Diseases: Methods, Challenges, and Future Directions," recently published in Cardiovascular Research. In this comprehensive review, we explore the latest advancements in molecular approaches—ranging from gene replacement to prime editing—and the various vectors used in cardiac gene therapy. We delve into critical strategies to improve genetic constructs, including promoter engineering, miRNA-regulated genetic cassettes, and systems for conditional expression of siRNAs/mRNAs. Additionally, we address the key factors that could facilitate the clinical translation of cardiac gene therapy, emphasizing research that suggests that even a limited percentage of transduced cardiomyocytes may be enough to halt or reverse the progression of certain cardiac genetic diseases. Our focus throughout the review is the progress of gene therapies for inherited arrhythmia syndromes and genetic cardiomyopathies, conditions for which few effective treatment options currently exist. These life-threatening disorders demand urgent therapeutic innovations. A heartfelt thanks to my mentor, Silvia Giuliana Priori, for her guidance, and to my friends and colleagues, Matteo Gianeselli, MD and Rossana Bongianino, who co-authored the manuscript. https://lnkd.in/dy6-bkDP

Duchenne muscular dystrophy (DMD) is a severe, rapidly progressive muscular dystrophy that primarily affects boys. It is caused by mutations in the genus DMD (dystrophin) that cause muscle weakness and atrophy of skeletal, smooth and CARDIAC muscles. The DMD gene, encoded in Xp21.2-p21.1, generates a large protein containing an N-terminal actin-binding domain and multiple spectrum repeats. The protein forms a component of the dystrophin-glycoprotein complex (DGC), which links the internal cytoskeleton and extracellular matrix. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (NMJ) and at a variety of synapses in the peripheral and central nervous systems and has a structural function in stabilizing the sarcolemma. Also implicated in signaling events and synaptic transmission. Deletions, duplications and point mutations at this genetic locus can cause Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD) or cardiomyopathy. The use of alternative promoters and alternative splicing results in numerous distinct transcript variants and protein isoforms. Fordadistrogene movaparvovec, Pfizer, is a recombinant adeno-associated virus, serotype 9 (AAV9) carrying a mini-dystrophin or truncated human dystrophin gene under the control of a muscle-specific promoter. The gene therapy is a mini-dystrophin because the human dystrophin gene is too large to fit in the AAV9 capsid. All patients needed to be negative for nAbs against AAV9 A fatal serious adverse event was reported as cardiac arrest for a participant in the Phase II DAYLIGHT study. DAYLIGHT is a single-arm, non-randomized, open-label study that includes boys who are at least two years old and less than four years old (including three-year-olds up until their fourth birthday). https://lnkd.in/ecU4VQAa

Exciting news from the Myology 2024 conference! The international gene therapy trial for Duchenne Muscular Dystrophy (DMD) using GNT0004 has unveiled promising findings. Led by Professor @Francesco Muntoni, the trial combines phases I to III with a dose escalation stage, followed by a pivotal phase. Enrolling ambulant boys aged 6 to 10 with DMD, the trial has received approval from French and UK authorities. Five patients have been administered GNT0004, demonstrating good tolerability and immunological response. Initial efficacy results for the patient receiving the higher dose (3×10^13 vg/kg) after one year showed clinical improvement, including an inflection in the North Star Ambulatory Assessment score. Other functional assessments also displayed positive trends. The safety and efficacy data have enabled Genethon, the trial’s sponsor, to prepare the pivotal European phase with the European Medicines Agency (EMA). GNT0004 is an AAV8 gene therapy that targets key tissues like skeletal and cardiac muscles through a single intravenous injection. DMD is a rare genetic disease that affects muscle function, and its absence leads to muscle degeneration and complications such as cardiomyopathy and loss of mobility. The trial’s progress represents a significant step towards potential therapeutic options for DMD.

🌟 𝗙𝗗𝗔 𝗔𝗽𝗽𝗿𝗼𝘃𝗲𝘀 𝗘𝗟𝗘𝗩𝗜𝗗𝗬𝗦 𝗚𝗲𝗻𝗲 𝗧𝗵𝗲𝗿𝗮𝗽𝘆 𝗳𝗼𝗿 𝗗𝘂𝗰𝗵𝗲𝗻𝗻𝗲 𝗠𝘂𝘀𝗰𝘂𝗹𝗮𝗿 𝗗𝘆𝘀𝘁𝗿𝗼𝗽𝗵𝘆 (𝗗𝗠𝗗) 🌟 The FDA's recent approval of ELEVIDYS (delandistrogene moxeparvovec-rokl), a gene therapy developed by Sarepta Therapeutics, marks a significant advancement in the treatment of Duchenne muscular dystrophy (DMD). This therapy is specifically designed for children aged 4 to 5 years with a confirmed mutation in the DMD gene. Patient associations highlight the importance of this milestone. As Pat Furlong, CEO of Parent Project Muscular Dystrophy (PPMD), noted, "Today’s decision marks an important moment in gene therapy for patients living with Duchenne. It’s been the lifelong work of so many in the Duchenne community. Our work continues until all patients in our community have access to therapy". The success of ELEVIDYS paves the way for further advancements in gene therapy, highlighting the importance of continued investment  in research for rare diseases. It underscores the potential of gene therapy to address other genetic disorders, offering a glimpse into a future where such innovative treatments could become standard care for a variety of conditions. This milestone fuels optimism among patients and researchers, reinforcing the belief that persistent scientific effort can lead to groundbreaking treatments and improved outcomes for those affected by rare diseases. For more detailed information, you can visit the - https://lnkd.in/eFpyXbFA -  https://lnkd.in/g5d2mqwj #GeneTherapy #DuchenneMuscularDystrophy #DMD #FDAApproval #HealthcareInnovation #RareDiseases #HopeForPatients

Cells collected from 1st SCD patient receiving bluebird bio's new SCD gene therapy, Lyfgenia Following their recent FDA approval and more than a decade of development, biotech firm Bluebird Bio has announced the completion of its first cell collection for their Sickle Cell Disease gene therapy, Lyfgenia. Designed for SCD patients aged 12 and older with a history of vaso-occlusive events (VOEs), Lyfgenia modifies patients' stem cells to produce HbAT87Q, a hemoglobin variant resistant to clumping. The treatment involves the collection and treatment of blood cell precursors, followed by reinfusion via a stem cell transplant - helping limit patient red blood cell sickling and potentially reducing the frequency and severity of VOEs. The Phase 1/2 trial showed 94% of patients had no severe VOEs post-treatment, with Bluebird Bio planning to conduct Phase 3 and long-term follow-up trials to further evaluate the therapy's safety and efficacy. The OxyDial team is thrilled to see this progress, and extends our congratulations to the Bluebird Bio team. We're thrilled to see continued advancements and novel therapies for genetic disorders like SCD, and hope to see more innovative treatments that improve the lives of patients worldwide. Read more: https://lnkd.in/etQRzPmT #SickleCellDisease #SCDgenetherapy #Lyfgenia #BluebirdBio #CureForSCD #HbAT87Q #PrecisionMedicine

One step forward in the right direction! Another first: Cleveland Clinic has performed the world's first in-human gene therapy for hypertrophic cardiomyopathy (HCM) as part of a clinical trial. Hypertrophic cardiomyopathy is a complex type of heart disease that affects an estimated 600,000 to 1.5 million Americans, or one in 500 people, but many of those patients go undiagnosed until the disease has progressed. The cause of hypertrophic cardiomyopathy may be unknown or attributed to genetics, high blood pressure or aging, making it difficult to identify a high-risk population. While most people with hypertrophic cardiomyopathy have a low risk for sudden cardiac death, the condition is the most common cause of sudden cardiac death in people under age 30. “Our understanding of HCM has progressed and we are excited to be a part of combining that knowledge with technology like gene therapy to further it even more,” said Milind Desai MD MBA, director of the Hypertrophic Cardiomyopathy Center at Cleveland Clinic, vice chair, Heart, Vascular & Thoracic Institute, Cleveland Clinic and Haslam Family Endowed Chair in Cardiovascular Medicine. Dr. Desai is an investigator for the MyPeak-1 Phase 1b clinical trial. “We look forward to continuing to study this therapy that involves a patient population that is often underdiagnosed and can suffer debilitating symptoms and sudden death.” Learn more about this first-of-its kind research: https://lnkd.in/gv3tmTAB #clevelandclinic #heartresearch #innovation #GivingDoesGood

FDA expands approval of gene therapy for patients with Duchenne muscular dystrophy FDA has expanded its approval of delandistrogene moxeparvovec-rokl (Elevidys—Sarepta Therapeutics), a recombinant gene therapy, to treat Duchenne muscular dystrophy (DMD). The debilitating disease most often affects males and is characterized by muscle weakness that eventually causes mobility limitations and cardiac or respiratory problems, among other issues. I.V. Elevidys treats the condition by delivering a gene that stimulates production of micro-dystrophin, which contains selected domains of the dystrophin protein found in healthy muscle cells. While the therapy was previously approved only for ambulatory patients aged 4-5 years of age with a confirmed mutation in the DMD gene, the expanded indication includes both ambulatory and non-ambulatory patients aged 4 years and older with a confirmed mutation in the DMD gene. FDA based the decision on trial results submitted by the manufacturer, the life-threatening nature of the disease, and the dearth of effective medical interventions — which it found outweighed the potential risks of the therapy. https://lnkd.in/gCiuijUv

Exciting news from in the world of gene therapy! Physicians have collected stem cells from a young boy with sickle cell disease in preparation for the first commercial infusion of Bluebird bio's newly approved gene therapy, Lyfgenia. This personalized treatment involves modifying the patient's own stem cells to produce a corrected form of the defective protein responsible for sickle cell disease. The process, from cell collection to infusion, takes 70-105 days. Bluebird bio is in talks to develop outcomes-based payment models with payers and with aid from the federal government to make Lyfgenia accessible through Medicare. While there is progress being made from access side, challenges remain in the complex and lengthy treatment process, including multiple cell collections, preconditioning chemotherapy, potential side effects like infertility, and complex logistics. However, this development represents a significant milestone in sickle cell treatment, offering hope for a more effective and potentially curative approach. Stay tuned for further advancements in gene therapies like Lyfgenia, revolutionizing the landscape of genetic disease treatment. #GeneTherapy #SickleCellDisease #HealthcareInnovation https://lnkd.in/e6B73-BA

Exploring the Future of Cell and Gene Therapy: Insights and Trends for 2024 and Beyond The field of cell and gene therapy (CGT) is rapidly evolving, and its impact on treating cancers and rare diseases is becoming increasingly significant. Here's a brief overview of the recent advancements and future projections in this dynamic sector: * Costs and Market Growth: CGT treatments, despite being costly (ranging from $400,000 to $2 million per dose), are expected to see a market surge, growing from $5.3 billion in 2022 to $19.9 billion by 2027. * FDA Approvals: 2023 witnessed a breakthrough with seven FDA approvals in the U.S. and one in the EU. Over 2,000 clinical trials are currently underway, with around 10% in Phase III, indicating a rapid pace towards more approvals. * Developments in 2024: Projections for 2024 include potentially 17 approvals in the U.S. and EU. There's excitement around the first-ever approval of adoptive cell therapy for solid tumors and the U.S. approval of allogeneic T-cell therapy. * The Role of AI: AI's influence in CGT R&D is growing, especially in target identification and payload design optimization. It's paving the way for more efficient and effective therapies. * Manufacturing Challenges: Consistency and quality in manufacturing remain key challenges. Innovations in on-chip technologies and imaging systems are aiding in addressing these issues. To stay updated with the latest news and developments in the laboratory equipment market, I encourage you to sign up for the Laboratory Equipment eNewsletter https://lnkd.in/eZ37Yr-u. These newsletters offer valuable insights and updates that can help you stay ahead in this rapidly evolving field. This post has been crafted with the assistance of ChatGPT. #CellAndGeneTherapy #CGT #FDAApprovals #ArtificialIntelligence #LabEquipment #HealthcareInnovation