Gene therapy has shown promising results in treating cases of myotubular myopathy, a rare disease that affects the muscles of young children.
- Myotubular myopathy affects one in 50,000 children, most often from birth or in the first months of life. Half of affected children die before the age of 18 months and three-quarters before the age of 10. It affects almost only boys, because the P1T1 gene which codes for myotubularin is carried on the X chromosome.
- Gene therapy involves introducing genetic material into cells to treat a disease. According to Inserm, around 700 clinical trials of gene therapy, all pathologies combined, have taken place or are underway around the world, including around thirty in France.
- Five years after the start of this clinical trial on 24 children, 16 of them were able to do without respiratory assistance in the weeks following treatment, 20 could sit for at least 30 seconds and, among them, 12 could stand up. alone and 8 can walk without support.
Myotubular myopathy is a rare genetic disease characterized by severe muscle weakness that can cause breathing problems and difficulty eating. Often fatal, it affects one in 50,000 children, only boys and most often from birth or the first months of life.
There is no treatment to date, but the results of a gene therapy trial, published in the journal The Lancet Neurologycould well change the situation.
Myotubular myopathy, a genetic anomaly
The clinical trial was conducted in 2017 by Astellas Gene Thérapies in six research centers around the world, with a test drug designed by the Généthon laboratory. While myotubular myopathy is due to abnormalities in the MTM1 gene which makes it possible to produce myotubularin, a protein essential to muscle cells, this gene therapy associates a viral vector (AAV8) with the M1T1 gene to “carry” the latter into the muscles.
In total, 24 children under 6 years of age suffering from myotubular myopathy were treated in two cohorts: 7 of them at a first dose, 17 others at a second, higher dose. Among them, a young patient received an injection of the drug I-Motionpediatric clinical trials center of the Institute of Myology, in Paris.
Children less affected by the disease… and side effects
Five years after the start of the trial, 16 children were able to do without respiratory assistance (previously essential 22 hours a day) in the 14 to 97 weeks after treatment, 20 children can sit up for at least 30 seconds and, among them, 12 can stand up independently and 8 can walk without support, whereas no child could do this before treatment.
Good results were nevertheless marred by side effects which caused the death of 4 children who showed signs of pre-existing hepatobiliary pathology. The trial was suspended while the origin of these complications was understood.
A potential first treatment for myotubular myopathy
“Even though we absolutely must understand the reasons for these side effects, it is exceptional to see children who were known to be doomed make incredible progress thanks to this drug candidate”underlines Ana Buj-Bello, researcher at Généthon, research director at Inserm and first author of the study.
In a Press releasethe Institute of Myology publishes a video showing the progress of Jules, the young French patient who received the innovative treatment in 2020. He who was “prisoner of his body” since his birth in 2016 can now breathe without assistance, walk, cycle…
“These clinical results show both how spectacularly effective gene therapy can be and the challenges that remain to be met, particularly in the area of side effects”agrees Frédéric Revah, general director of Généthon, who welcomes the work “rich in teaching for the entire scientific community” And “a potential first treatment for this rare and deadly disease”.
