Genetic treatments in muscular dystrophies

The search for a cure for Duchenne muscular dystrophy and other muscular dystrophies is progressing rapidly despite significant challenges posed by some genes and the complexity of targeting all skeletal muscles. This review focuses on three areas in which experimental clinical studies are in progress.

Two Phase I/IIa gene-therapy trials using adeno-associated viral vectors have recently started, one in limb-girdle muscular dystrophy and one in Duchenne muscular dystrophy. They will assess the safety of the intramuscular administration of the relevant adeno-associated viral vectors, and local efficacy. Two more Phase I/IIa studies are underway in Duchenne muscular dystrophy, focused on the intramuscular administration of antisense oligonucleotides to induce exon skipping. A third study is evaluating efficacy and tolerability of a drug which induces read-through of stop codons in Duchenne muscular dystrophy patients carrying nonsense mutations.

These studies should provide proof of principle of these experimental approaches in humans. It is likely that further refinement will be required before extending their use to the wider community of patients with muscular dystrophy. In the meantime it is important to prepare accurate registries of molecularly characterized patients to facilitate their recruitment in future studies.