February 5th, 2014
Audentes Therapeutics, Inc., a biotechnology company dedicated to the development of innovative treatments for rare muscle diseases, and Genethon, a non-profit organization dedicated to the research and development of biotherapies for orphan genetic diseases, announce that they have entered into an agreement to develop AT001 for the treatment of X-Linked Myotubular Myopathy (XLMTM), a rare, inherited disorder characterized by severe muscle weakness and respiratory impairment. 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 (Buj-Bello et al, Human Molecular Genetics, 2008, Vol. 17: 2132-2143; Buj-Bello et al, Molecular Therapy, 2013, 21:sup 1, S14). 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 (Childers et al., Science Translational Medicine, 22 January 2014 6:220ra10). 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.