Statistical correlation between strength and mini-dystrophin expression in skeletal muscle after an rAAV9-mini-dystrophin gene therapy candidate in DMDmdx rats.

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder resulting from loss-of-function mutations in the dystrophin gene, leading to progressive muscle wasting and premature death. We present the mini-dystrophin protein expression-function relationship from a post-hoc analysis of mini-dystrophin quantification and function (strength) data at 3 and 6 months in biceps femoris and pectoralis muscles from a DMD rat model (DMDmdx) treated with fordadistrogene movaparvovec, an adeno-associated virus serotype 9 gene therapy containing miniaturised dystrophin. Four treatment groups of ~7-9-week-old DMDmdx rats and two control groups (one wild-type and one DMDmdx group) of ~7-9-week-old DMDmdx rats received fordadistrogene movaparvovec (1E + 13, 3E + 13, 1E + 14 or 3E + 14 vg/kg) or formulation buffer, respectively. Muscle samples were harvested at 3 or 6 months post-administration. Previously reported treatment of DMDmdx rats with fordadistrogene movaparvovec increased body weight, improved clinical chemistry parameters, ameliorated skeletal and cardiac muscle histopathology and improved muscle and cardiac function, all in a dose-dependent manner. Data from this post-hoc analysis indicate that expression of the mini-dystrophin protein levels is sustained or increased (at lower doses) from 3 to 6 months post-dose in DMDmdx rats treated with fordadistrogene movaparvovec. Taken together, this suggests a correlation between mini-dystrophin protein expression and function in the DMDmdx rat model 3 and 6 months after fordadistrogene movaparvovec.