Potential therapies in development

Developing potential new therapies to target XLMTM

Several potential therapies are being investigated for the treatment of X-linked myotubular myopathy (XLMTM), some of which target the underlying cause of disease.1,2 Because XLMTM is caused by mutations in the MTM1 gene leading to myotubularin deficiency, myotubularin and its substrates, or other interacting proteins, have been the focus of emerging therapeutic approaches.

Potential therapies in clinical phase:

Gene replacement therapy of MTM1

Gene therapies aiming to introduce a functional copy of MTM1 are currently in clinical development for XLMTM.1,2

Modulation of Dynamin-2

Dynamin-2—a GTP-binding protein associated with microtubules—has been found to be dysregulated in several centronuclear myopathies (CNMs), including XLMTM, and may function in the same or related signaling pathway as myotubularin.1

Potential therapies in preclinical phase:

Estrogen modulation using tamoxifen

Tamoxifen has been shown to improve muscle pathology and strength in mouse models of XLMTM, and investigation for clinical use is anticipated.3,4

Modulation of PI3K

Phosphoinositide 3-kinase (PI3K)—a signaling protein—has been found to be dysregulated in several centronuclear myopathies, including XLMTM, and may function in the same or related signaling pathway as myotubularin.1

Inhibition of PIK3C2B or acetylcholinesterase

Inhibition of phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 beta (PIK3C2B, a member of the PI3K protein family) and acetylcholinesterase (AChE, an enzyme that processes neurotransmitters) have been shown to improve symptoms of neuromuscular disorder in animal models of XLMTM.1,5

Enzyme or protein replacement

Targeting myotubularin in mouse models of XLMTM has been shown to improve muscle weakness and pathology.1,6

Myoblast transplantation

Syngeneic myoblast transplantation of healthy donor cells into a mouse model of XLMTM has been shown to improve muscle function.1,7

Additional resources and materials are available to help support you and your patients in managing XLMTM.


1. Zanoteli E. Expert Opin Orphan Drugs. 2018;6(6):375-384. 2. Audentes Therapeutics. NLM identifier: NCT03199469. Accessed April 10, 2020. 3. Gayi E, et al. Nat Commun. 2018;9(1):4848. 4. Maani N, et al. Nat Commun. 2018;9(1):4849. 5. Sabha N, et al. J Clin Invest. 2016;126(9):3613-3625. 6. Lawlor MW, et al. Human Mol Genet. 2013;22(8):1525-1538. 7. Lim HJ, et al. Cell Transplant. 2015;24:1887-1900.


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