Exon-specific dystrophin antibodies for studies of Duchenne muscular dystrophy

Abstract

AbstractExon-specific anti-dystrophin antibodies are used to monitor the success of treatments for Duchenne muscular dystrophy that aim to restore the missing dystrophin protein. Dystrophin is a large cytoskeletal protein encoded by 79 exons and expressed mainly in muscle. Most cases of Duchenne and Becker muscular dystrophies are caused by genetic deletion of one or more exons. In-frame deletions permit some synthesis of internally-deleted dystrophin and cause the milder Becker form, while out-of-frame deletions in the severe Duchenne form result in early stop-codons and no functional dystrophin synthesis. In this study, we describe the production of ten new monoclonal antibodies against a rod region encoded by exons 55–59 and their mapping to specific dystrophin exons, thus filling a major gap in the spectrum of available antibodies. The antibodies have already been applied in a published clinical trial of a drug treatment for Duchenne muscular dystrophy.