The Hospital for Sick Children

Published purpose

Myotubular myopathy is a severe congenital disorder marked by muscle weakness and hypotonia due to mutations in the MTM1 gene, which encodes myotubularin. This protein is crucial for muscle cell maintenance and repair, and its deficiency disrupts these processes, causing significant muscle dysfunction. Current treatments are symptomatic and fail to address the genetic cause, necessitating therapies that target the root of the disease. Gene therapy, particularly with viral vectors, shows promise but has limitations such as immune responses and high costs. Recent safety setbacks in AAV8-MTM1 gene therapy trials underscore the need for alternative delivery methods. Lipid nanoparticles (LNPs), successful in mRNA vaccine delivery, offer a promising non-viral alternative. NRC’s proprietary LNPs, targeted to skeletal muscle cells, present an innovative solution. This project hypothesizes that LNP-mediated delivery of a functional MTM1 gene can restore myotubularin function, enhancing muscle strength and function in myotubular myopathy patients without the risks associated with viral vectors.