Promising preclinical data recently published in Science Translational Medicine, Audentes Therapeutics Inc. and Genethon announce that they have entered into an agreement to develop AT001 for the treatment of Myotubular Myopathy
A significant step forward
“Our agreement with Genethon is a significant step forward towards the development of a treatment for patients with this serious, rare disease,” said Matthew R. Patterson, President and CEO of Audentes. “The combination of Genethon’s expertise in the manufacturing and development of gene therapy products and Audentes’ world-class orphan drug development team will allow us to rapidly advance this program.”
A potential treatment using gene therapy technology
AT001 is a novel drug candidate based on adeno-associated virus (AAV) gene therapy technology.The development of a potential treatment for XLMTM using gene therapy technology was initiated at Genethon in 2009. Studies by Buj-Bello et al in a mouse model of the disease demonstrated that delivery of the deficient gene using an AAV vector system resulted in increased expression of the protein, improvement in muscle architecture, reversal of muscle hypotrophy, improvement in muscle strength, and an improvement in overall survival
The first demonstration of persistent disease correction
More recently, collaborators at Genethon, the University of Washington and Harvard University announced promising results from studies of the same treatment approach in a naturally-occurring dog model of XLMTM. These studies demonstrated that treatment with a single dose of AAV carrying the gene deficient in XLMTM resulted in an increase in muscle strength, improved respiratory function, and prolonged survival. These data are the first demonstration of persistent disease correction in a large animal model of a neuromuscular disease through the delivery of a single, intravenous administration of AAV.
X-Linked Myotubular Myopathy (XLMTM) is a rare, inherited disorder characterized by severe muscle weakness and respiratory impairment. It is caused by mutations in the MTM1 gene, which encodes an enzyme called myotubularin. Myotubularin is thought to be involved in the development and maintenance of muscle cells. XLMTM affects 1 in 50,000 newborn males worldwide. In a majority of newborns with the disorder, XLMTM causes death in the first years of life. There is currently no effective treatment for this disease.
