Gene therapy of myotubular myopathy

Muscle disease is treated with gene therapy

Kirill Stasevich, Science and Life (nkj.ru ), based on materials Science

Myopathies are a whole group of diseases affecting the muscles and nerves that control them. Among myopathies, there are congenital ones, such as myotubular myopathy – it occurs only in men (with a probability of about 1 in 50,000 births) and occurs due to a defect in the MTM1 gene, which is located on the X chromosome. 

The MTM1 gene encodes the enzyme myotubularin, which is necessary for the normal development of muscle tissue. Boys with this myopathy do not just have reduced muscle tone – they sometimes cannot breathe and swallow themselves, so they have to be connected to life support devices. Few reach the age of ten, and half of the patients die after living barely a year and a half.

However, researchers from the University of California at Los Angeles, the Ann and Robert H. Lurie Children's Hospital in Chicago and other research centers in the USA, Canada, Germany and France with the help of gene therapy have managed to significantly improve the condition of nine children with myotubular myopathy. 

Modified particles of the adenoassociated virus were injected into sick boys aged 8 months to 6 years. This virus embeds its genome into human DNA without causing any problems for the host, so it is often used in molecular genetic procedures with human and primate cells.

This time, the virus was loaded with the normal MTM1 gene, from which muscle cells had to synthesize the necessary myotubularin for them. The biopsy showed that two days later the enzyme appeared in the muscles of the lower leg, and not just appeared – the level of myotubularin was 85% of normal. 

The underdeveloped muscle fibers began to increase, and after a few months, four boys could already sit by themselves, and three could even walk without support; some learned to make sounds themselves with their mouth and throat, which they had not been able to do before (after all, you also need to work muscles for the voice). And although they still need to be fed through a special tube, some have started eating themselves. Three patients, however, had severe side effects, but these effects were suppressed.

The researchers reported the results at the annual conference of the American Society for Gene and Cell Therapy. In animal experiments, the gene introduced from the outside has been working for several years, but even if the gene needs to be introduced periodically, this does not detract from the effect achieved.

Gene therapy has recently been increasingly used against neuromuscular diseases: there are cases when it has been possible to help patients with spinal muscular atrophy, Duchenne myodystrophy, limb-girdle muscular dystrophy in this way. 

And neuromuscular disorders are not limited here: for example, two years ago we wrote about how a boy with a very severe hereditary disease literally managed to give a new skin.

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