Dystrophin Analysis in Clinical Trials

Abstract

Duchenne muscular dystrophy (DMD) is a severe muscle-wasting disease with unmet medical need. The disease is caused by mutations that disrupt the open reading frame of the dystrophin protein that is required to maintain muscle fiber stability during contraction. Lacking dystrophin patients' muscle fibers are continuously damaged eventually leading to replacement of muscle tissue by fibrotic and adipose tissues and loss of muscle function. Many therapeutic approaches aiming at dystrophin restoration are in development, and some have been or are being tested in clinical trials. For these approaches, showing dystrophin restoration or increased dystrophin expression could serve as a pharmacodynamic biomarker to confirm mechanism of action. This review provides an overview of methods currently in use to assess dystrophin in clinical trial muscle biopsies and discusses challenges of dystrophin quantification and using dystrophin as a biomarker in clinical trials.