Gene therapy has made it possible to restore normal muscle activity to animals suffering from myotubular myopathy. Human trials are expected to be conducted in 2015.
Promising advance against a very rare form of myopathy which affects one boy in 50,000 births. It is the congenital myotubular myopathy, a terrible disease which makes at birth, the child abnormally soft and in respiratory distress. The evolution is often quickly fatal. When respiratory resuscitation allows the child to pass the neonatal stage, he is likely to acquire sitting, standing and even walking very late.
“The quality of life for these children is terrible. As they cannot breathe, they have a tracheostomy and are constantly on respiratory assistance, which increases the risk of infection, says Professor Fulvio Mavilio, scientific director of Genethon, and a pioneer in the field of gene therapy. Until now, there was no cure, but researchers are on the trail of a very encouraging gene therapy.
The mutant gene has been replaced
This form of myopathy is caused by the mutation of a gene: the MTM1 gene, which enables the production of myotubularin, a protein important for muscle contraction. However, researchers have succeeded in replacing the mutated gene in animals suffering from this myopathy using a virus. The virus rendered harmless belongs to the adenovirus family, which have the particularity of having a DNA strand. The researchers modify this DNA, add the drug gene, a functional MTM1 gene. They inject a quantity of these modified viruses (AAVs) into the sick animal and the viruses carry the drug gene into the heart of muscle cells which can then produce myotubularin.
Listen to Prof. Fulvio Mavilio, scientific director of Généthon. ” The success in tubular myopathy is explained by the fact that the amount of protein (myotubularin) sufficient to treat the symptoms is very small: 5-10% of the normal amount is enough to restore function to the respiratory and skeletal muscles. “
From 2009 in the laboratories of Genethon in Evry, the team of Dr Anna Buj Bello, Inserm researcher, carried out the first studies of intravenous gene therapy on mice suffering from this myopathy.
2 treated dogs are almost normal
Their success led to the development of a study in dogs naturally carrying this genetic anomaly, with American teams from Boston and Seattle. The results have just been published in the journal Science Translational Medicine. “Two of the dogs treated with this AAV gene therapy appear almost normal, even at the microscopic level,” said Dr. Martin Childers of the University of Washington, the study’s first author. “These preclinical results are extraordinary for inherited muscle diseases. “(See the video)
Excellent news for Dr Anna Buj Bello, Principal Investigator at Genethon. “These results are the culmination of 4 years of research and show how effective gene therapy is in this genetic muscle disease. We can finally consider a clinical trial in patients. Perhaps by 2015, but there are still some pre-clinical steps to be taken, such as determining the tolerable dose of vector virus to be injected into humans.
Listen to Prof. Fulvio Mavilio, scientific director of Généthon. ” It is very impressive. I have never seen such results in terms of efficiency. This gives hope for other pathologies that can be treated with the same therapeutic approach. “
The scientific director of Généthon also underlined that these impressive results in the treatment of a rare disease were possible thanks to the donations obtained by the Telethon.
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