Developing a Gene Therapy for Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is a severe, progressive, fatal muscle disorder caused by loss-of-function mutations in the DMD gene that leads to the absence of the dystrophin protein. Without dystrophin, the structural link between the actin cytoskeleton and extracellular matrix is broken and muscles are highly susceptible to contraction-induced damage. Direct dystrophin replacement has thus far been unsuccessful due to the large size of the DMD gene. At present, there are only limited treatment options available to DMD patients.
Gene therapy is an approach that addresses the root cause of certain genetic diseases by replacing a non-functioning, mutated gene with a functional version. Adeno-associated virus (AAV) mediated gene therapy is an ideal treatment strategy to slow or even stop progression of the disease in most patients. AAV vectors are non-pathogenic viruses that have been designed to enable the safe, systemic, wide-spread delivery of a functional gene. However, there are significant limitations to use of AAV in gene therapy including its genome carrying capacity of approximately 5000 base pairs, ability to manufacture in large scale, and targeting of all affected tissues.
Solid Biosciences, a company focused solely on DMD, is developing an AAV micro-dystrophin vector (SGT-001) that may overcome many of the gene therapy barriers, including manufacturing, with the goal to enter clinical trials for DMD. The program is based on extensive research on the dystrophin protein to develop shorter yet functional micro-dystrophin variants that can fit into the AAV, and to deliver genes to the majority of affected muscles. Solid is developing SGT-001 as a viable therapeutic option for all DMD patients, regardless of mutation.