Testing AOC 1001 to Treat Myotonic Dystrophy Type 1 (DM1) скачать в хорошем качестве

Testing AOC 1001 to Treat Myotonic Dystrophy Type 1 (DM1)

Art Levin, PhD, distinguished scientist and strategic leader and member of the company’s board of directors at Avidity Biosciences, discusses positive data from the preliminary assessment of the phase 1/2 MARINA trial of AOC 1001 in patients with myotonic dystrophy type 1 (DM1). DM1 is a form of muscular dystrophy characterized by myotonia or the inability for muscles to relax, as well as muscle weakness. Other common symptoms include respiratory problems, fatigue, hypersomnia, cardiac abnormalities, severe gastrointestinal complications, and cognitive and behavioral impairment. DM1 is caused by a triplet-repeat in the DMPK gene, resulting in a toxic gain of function mRNA. Currently, there are no approved treatments for DM1. As Dr. Levin explains, MARINA is a randomized, double-blind, placebo-controlled, phase 1/2 study evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple-doses of AOC 1001 when administered intravenously to adult patients with DM1. AOC 1001 is a monoclonal antibody that binds to the transferrin receptor 1 (TfR1) conjugated with a siRNA targeting DMPK mRNA. Participants received a single dose of 1 mg/kg AOC 1001, two doses of 2 mg/kg AOC 1001, or placebo. The preliminary assessment includes biomarker data six weeks after dosing. Key findings include the demonstration of targeted delivery of 2 mg/kg AOC 1001 to muscle, a tissue previously untreatable with existing RNA therapeutics; meaningful DMPK reduction in 100% of participants treated with AOC 1001; a mean reduction of 45% in DMPK after only a single dose of 1 mg/kg or two doses of 2 mg/kg of AOC 1001; and splicing improvement of 31% in a key set of muscle-specific genes and of 16% across a broad 22-gene panel in the 2 mg/kg cohort (this indicates AOC 1001 activity in the nucleus). Finally, this assessment demonstrates early signs of clinical activity with improvement in myotonia in some participants and that AOC 1001 is safe and tolerable, with the majority of adverse events (AEs) being mild or moderate. To learn more about DM1 and other rare musculoskeletal diseases, visit checkrare.com/diseases/musculoskeletal