Coxen Hole

Researchers are evaluating the safety and tolerability of intramuscular gene therapy using AAV9-Follistatin, either alone or combined with a VEGF-encoding plasmid, in adults experiencing age-related muscle decline. This Phase 1/2a open-label, non-randomized study aims to assess preliminary biological and functional effects such as changes in muscle mass and performance. The study involves adults aged 45 to 75 years who have evidence of physical decline or a sedentary lifestyle and meet specific health criteria, including low antibody levels to the AAV vector. Participants will be assigned sequentially to one of three groups: low-dose AAV-Follistatin monotherapy, high-dose AAV-Follistatin monotherapy, or combination therapy with AAV-Follistatin plus VEGF plasmid. All treatments are given by intramuscular injection into large skeletal muscles. In the combination group, the VEGF plasmid is administered twice, followed by AAV-Follistatin about two weeks later. Rapamycin will be given for around two months to reduce immune responses to the gene therapy. The study uses a cautious dose-escalation design with sentinel dosing. Participants will undergo screening including medical history, physical exams, lab tests, and muscle assessments. The core study lasts about 90 days (120 days for combination therapy group) with regular safety checks and functional tests. Optional extended safety follow-up visits occur at about 6 and 12 months. Researchers will monitor adverse events, immune reactions, muscle strength, and other functional outcomes. Safety monitoring includes clinical assessments and laboratory testing. Total participation is approximately three months, with optional longer follow-up.