A team of researchers in France, led by Dr. Ana Buj–Bello (Genethon/Inserm) and teams at the University of Washington and Harvard Medical School in the United States, achieved a new step towards the treatment of myotubular myopathy by gene therapy. The researchers demonstrated the efficacy of administration of a therapeutic vector by a single intravenous injection and identified the dose that restores long–term muscular strength in a large animal model of the disease.

This work, published in the journal Molecular Therapy, has been achieved thanks to donations from the French Telethon and the support of the Myotubular Trust.

Myotubular myopathy is an X–linked genetic disease affecting 1 in 50,000 newborn boys. It is caused by mutations in the MTM1 gene encoding myotubularin, a protein involved in the functioning of muscle cells. The severe form of the disease leads to hypotonia, generalized muscle weakness and death in early infancy due to breathing difficulties. Dogs naturally affected by this myopathy also have a reduced life expectancy. To date, there is no effective treatment for this rare disease.

In the present study, Genethon’s team developed and manufactured an adeno–associated virus (AAV) vector able to deliver a normal copy of the MTM1 gene in the entire musculature. The AAV product was administrated by a simple intravenous injection in ten week–old dogs manifesting the first symptoms of the disease – instead of the locoregional route of administration used in previous studies.

The treatment restored whole–body muscle strength and function, and prolonged the life of affected dogs. Treated dogs were indistinguishable from normal animals 9 months after product injection.

Dr. Ana Buj–Bello, Genethon/Inserm said: « We report a dose–finding study and show the therapeutic benefit of the vector by a single intravenous injection. It is a clinically–relevant route of administration and represents a step towards a clinical trial in patients”.