New research brings hope for myotubular myopathy, by revealing how muscle cells control their growth

The laboratory of Dr Karim Hnia at INSERM in Toulouse recently published the findings of their investigation into the question, Is the mTORC1 pathway a route to treatment in x-linked myotubular myopathy (XLMTM)?

mTORC1 in our cells is a ‘master regulator’ of muscle growth – from early steps of muscle differentiation in the womb, to the work of muscles in adult life. The work of Dr Hnia’s laboratory had shown that mTORC1 is ‘overactivated’ when XLMTM is present, and the Myotubular Trust was delighted to support their laboratory’s work to further investigate whether the mTORC1 pathway could be a new route to potential treatments for XLMTM.

The findings of this 2 year project were published in the prestigious journal, Nature Metabolism, in March 2026.

Summary

Dr Karim Hnia said : “We discovered a new mechanism that muscle cells use to control their growth, involving MTM1 and a tiny compartment inside the cells called ‘lysosomes’. These lysosomes act like ‘decision hubs’ that help the cell decide when and how to grow.

In healthy muscle cells, MTM1 helps keep certain fats (phosphoinositides) on the surface of lysosomes in the right balance. When this balance is correct, the lysosome can switch on a major growth signal in the cell called mTORC1, which tells the muscle when to build and maintain its structure.

In myotubular myopathy, MTM1 doesn’t work properly. Because of that, the balance of those fats on the lysosome surface becomes disrupted. When this happens, the lysosome can’t activate mTORC1 as it should, meaning the muscle cell can’t properly control its growth or upkeep. This contributes directly to the muscle weakness seen in the disease.

In both cell and mouse models of Myotubular Myopathy, we restored the level of those fats (phosphoinositides) at the lysosome, and therefore normal mTORC1 activity, and this improved both muscle growth and maintenance. This finding uncovers a new metabolic checkpoint inside muscle cells, and brings real hope for designing targeted therapies for patients.” Read the full article in Nature journal, here.