Microdystrophin Expression As a Surrogate Endpoint for Duchenne Muscular Dystrophy Clinical Trials

Overview

Journal Hum Gene Ther

Specialties Genetics
Pharmacology

Date 2023 Jan 25

PMID 36694468

Authors

Jeffrey S Chamberlain

Melissa Robb

Serge Braun

Kristy J Brown

Olivier Danos

Annie Ganot

Pedro Gonzalez-Alegre

Nina Hunter

Craig McDonald

Carl Morris

Mark Tobolowsky

Kathryn R Wagner

Olivia Ziolkowski

Dongsheng Duan

Affiliations

Soon will be listed here.

Abstract

Duchenne muscular dystrophy (DMD) is a serious, rare genetic disease, affecting primarily boys. It is caused by mutations in the gene and is characterized by progressive muscle degeneration that results in loss of function and early death due to respiratory and/or cardiac failure. Although limited treatment options are available, some for only small subsets of the patient population, DMD remains a disease with large unmet medical needs. The adeno-associated virus (AAV) vector is the leading gene delivery system for addressing genetic neuromuscular diseases. Since the gene encoding the full-length dystrophin protein exceeds the packaging capacity of a single AAV vector, gene replacement therapy based on AAV-delivery of shortened, yet, functional microdystrophin genes has emerged as a promising treatment. This article seeks to explain the rationale for use of the accelerated approval pathway to advance AAV microdystrophin gene therapy for DMD. Specifically, we provide support for the use of microdystrophin expression as a surrogate endpoint that could be used in clinical trials to support accelerated approval.

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