SRK-015 improves Muscle Function and Biomarkers in the FLExDUX4.Cre Mouse Model of FSHD


Topic:

Translational Research

Poster Number: 301 T

Author(s):

Adam Fogel, PhD, Scholar Rock, Kaleigh Canonico, Scholar Rock, Christopher Chapron, Scholar Rock, Bimal Regmi, Scholar Rock, Jerod Hurst, Scholar Rock, Erin Lopez, Scholar Rock, Leslie Cortes, Scholar Rock, Jennifer Gilley, Myologica, Jennifer Martin, Myologica, Natania Kurien, Myologica, Ramzi Khairallah, Myologica, Mo Qatanani, Scholar Rock

Inhibition of myostatin activation with SRK-015 (apitegromab) is a promising muscle targeted approach for improving motor function in neuromuscular disorders. Apitegromab has demonstrated positive results in both preclinical models of Spinal Muscular Atrophy (SMA) and in a placebo-controlled phase III trial in SMA patients. Facioscapulohumeral muscular dystrophy (FSHD) is a neuromuscular disease in which sporadic DUX4 expression in myonuclei causes a patchy pattern of muscle fiber loss, with the unaffected motor units remaining intact. We hypothesized that selective myostatin inhibition with SRK-015 could improve muscle function in FSHD by enhancing these remaining motor units. We have studied the potential of SRK-015 in FSHD using the FLExDUX4.Cre mouse model, which recapitulates the patchy nature of muscle fiber loss and functional deficit observed in the disease. Treatment with SRK-015 drove improvements in muscle size, muscle function and running endurance in both male and female young FLExDUX4.Cre mice, as well as in aged mice. Positive effects with SRK-015 were also observed on muscle biomarkers and muscle cellular composition. These results support the continued investigation of apitegromab as an approach in FSHD.