X-linked myotubular myopathy, liver disease, and gene therapy.

Abstract

X-linked myotubular myopathy (XLMTM) is a rare and severe neuromuscular disorder commonly characterized by profound skeletal muscle weakness, significant co-morbid disabilities, and early death. XLMTM has traditionally been viewed as primarily a disorder of skeletal muscle. However, there is an emerging appreciation of extra-muscular symptom involvement in XLMTM, most notably hepatobiliary disease. As promising genetic therapies for XLMTM rapidly advance, incomplete understanding of these manifestations has presented a significant barrier to safe and effective clinical translation, as well limited understanding of disease management and patient outcomes. In this review, we provide an update on the recent advances in XLMTM drug development, examine emerging data on XLMTM-associated liver disease and its impact on therapeutic development, and discuss future directions for understanding and targeting the serious non-muscle manifestations of this disorder.