Astellas Gene Therapies is developing AT132 for the treatment of X-Linked Myotubular Myopathy.

X-linked Myotubular Myopathy (XLMTM) is a serious, life-threatening, rare neuromuscular disease that is characterized by extreme muscle weakness, respiratory failure and early death. Mortality rates are estimated to be 50 percent in the first 18 months of life, and for those patients who survive past infancy, approximately 75 percent will live to the age of 10. XLMTM is caused by mutations in the MTM1 gene that lead to a lack or dysfunction of myotubularin, a protein that is needed for normal development, maturation, and function of skeletal muscle cells. The disease affects approximately 1 in 40,000 to 50,000 newborn males.

XLMTM places a substantial burden on the healthcare system, including high rates of healthcare utilization, hospitalization and surgical intervention. More than 80 percent of XLMTM patients require ventilator support, and the majority of patients require a gastrostomy tube for nutritional support. In most patients, normal developmental motor milestones are delayed or never achieved. Currently, only supportive treatment options, such as ventilator use or a feeding tube, are available.

Astellas Gene Therapies is developing the novel product candidate AT132, an AAV8 vector containing a functional copy of the MTM1 gene, for the treatment of XLMTM.

The preclinical development of AT132 was conducted in collaboration with Genethon.

AT132 has been granted Regenerative Medicine and Advanced Therapy (RMAT), Rare Pediatric Disease, Fast Track and Orphan Drug designations by the U.S. Food and Drug Administration (FDA), and Priority Medicines (PRIME) and Orphan Drug designations by the European Medicines Agency (EMA).

X-linked Myotubular Myopathy (XLMTM)

X-linked myotubular myopathy (XLMTM) is a life-threatening neuromuscular disorder requiring early and intensive medical intervention from birth1. Approximately 1 in 40,000 to 50,000 newborn males have the condition2. XLMTM is caused by mutations in the MTM1 gene that result in the absence of, or dysfunctional, myotubularin protein. Symptoms include profound muscle weakness and hypotonia, feeding difficulties and severe respiratory insufficiency3. About 50 percent of patients die in the first 18 months of life due to respiratory failure or related complications4.

Our approach: we are developing an AAV gene replacement therapy to deliver a functional copy of the MTM1 gene into skeletal muscle cells to produce the missing myotubularin protein. If you are a U.S. based physician, and would like more information about XLMTM, please visit: https://xlmtm.com/

References

  1. Guan, Xuan, et al. “Gene therapy in monogenic congenital myopathies.” Methods 99 (2016): 91-98.
  2. Jungbluth, Heinz, Carina Wallgren-Pettersson, and Jocelyn Laporte. “Centronuclear (myotubular) myopathy.” Orphanet journal of rare diseases 3.1 (2008): 26.
  3. McEntagart M, Parsons G, Buj-Bello A, et al. Genotype-phenotype correlations in x-linked myotubular myopathy. Neuromuscul Disord. 2002;12(10):939-46.
  4. Beggs AH, Byrne BJ, De Chastonay S, et al. A multicenter, retrospective medical record review of X-linked myotubular myopathy: The recensus study. Muscle Nerve. 2018;57(4):550-560. doi:10.1002/mus.26018