A novel gene therapy approach that is competent of transporting unabridged editions of large genes and enhancing skeleton muscle function could hold new hope for treating dysferlinopathies and other muscular dystrophies, say researchers from The Research Institute of Nationwide Children’s Hospital.
Dysferlinopathies, a cluster of incurable muscle disorders occurred due to mutations in the dysferlin gene.
People suffering these disorders, counting limb girdle muscular dystrophy type 2B, are normally diagnosed in their early twenties. About one-third of the patients become wheelchair dependent by their mid thirties. Gene therapy which uses adeno-associated virus (AAV) to transport genes to cells has been trailed as an alternative for some patients with muscular dystrophy.
Principal investigator Dr Louise Rodino-Klapac, from the Center for Gene Therapy and colleagues, carried out mice study in which they used AAV5 to package a full-length, intact dysferlin gene and straightforwardly deliver it to the diaphragm of mice deficient of dysferlin. They also injected the leg muscle of mice with the help of intramuscular and vascular approaches.
They did that in order to further determine whether the gene delivery could improve function of skeletal muscles. The team found that the intravascular as well as intramuscular delivery approaches escorted to full-length, intact dysferlin gene expression in the leg and cells of diaphragm muscle of the mice.
More significantly, they found that the newly-restored dysferlin repaired membrane deficits earlier seen in the mice deficient of dysferlin. Dr Rodino-Klapac, explained the study findings exhibit highly favorable results with full restoration of dysferlin without compromise in function. With regard to neuromuscular diseases, these studies provide new perspective for conditions caused by mutations of large genes.
She added Duchenne muscular dystrophy is the most common severe childhood muscular dystrophy and would seem to benefit from expression of the larger transcripts than mini- and micro-dystrophins that only partially restore physiologic function in mouse models of the disease. They have shown that AAV5-dysferlin delivery is a very promising therapeutic approach that could restore functional deficits in dysferlinopathy patients.
The study was reported in the PLoS ONE.