Monitoring Duchenne Muscular Dystrophy Gene Therapy with Epitope-Specific Monoclonal Antibodies

Abstract

Several molecular approaches to Duchenne muscular dystrophy (DMD) therapy are at or near the point of clinical trial and usually involve attempts to replace the missing dystrophin protein. Although improved muscle function is the ultimate measure of success, assessment of dystrophin levels after therapy is essential to determine whether any improved function is a direct consequence of the treatment or, in the absence of improved function, to determine whether new dystrophin is present, though ineffective. The choice of a monoclonal antibody (mAb) to distinguish successful therapy from naturally occurring “revertant” fibres depends on which dystrophin exons are deleted in the DMD patient. Over the past 20 years, we have produced over 150 “exon-specific” mAbs, mapped them to different regions of dystrophin and made them available through the MDA Monoclonal Antibody Resource for research and for clinical trials tailored to individual patients. In this protocol, we describe the use of these mAb to monitor DMD gene therapy.