A gene therapy approach for treating Duchenne muscular dystrophy that reduces symptoms in canine models of the disease is reported in Nature Communications this week. The research demonstrates that this approach is safe and effective in reducing muscle symptoms in this disorder.
Duchenne muscular dystrophy is an inherited disease that mainly affects boys and is caused by defects in a gene coding for a protein called dystrophin. Without dystrophin, skeletal muscles and the heart degenerate so that patients become confined to a wheelchair and usually die before the age of 30. Gene transfer therapies using adeno-associated viral (AAV) vectors are an efficient method for replacing other faulty genes in skeletal muscle, but the size of the dystrophin gene is too large and exceeds the packaging capacity of this vector. One approach is to use a truncated but partially functional dystrophin gene, called microdystrophin, but previous studies have relied on using immunosuppressants, which may carry health risks.
George Dickson, Caroline Le Guiner and colleagues test this approach without the use of immunosuppressants in 12 golden retriever muscular dystrophy dogs, a large animal model of Duchenne muscular dystrophy that is considered a valuable preclinical platform to test gene therapy strategies. They show that local and systemic delivery of a modified AAV vector carrying microdystrophin is effective in restoring dystrophin expression and stabilizing clinical symptoms up to 26 months of age, without requiring immunosuppression. These results demonstrate the safety of this approach in large animal models of Duchenne muscular dystrophy, and may pave the way towards clinical trials in patients.