Effective treatment in some patients with a type of Charcot-Marie-Tooth disease, the most common hereditary neurological disorders (30,000 patients in France), has just been found.
"Yes, finally! For the first time since our pathology was identified – a hundred thirty-three years ago! – a serious hope for the treatment of the effects has just come true." This call from the heart is pushed by Martine Libany and Daniel Tanesse, voluntary organizers of the XXIXe National congress of the Charcot-Marie-Tooth association of people affected by the disease, CMT France, which will take place in Montpellier on 30 March (www.cmt-france.org).
CMT is a disease that has long been considered as non-changing life expectancy (not to be confused with Charcot's disease or amyotrophic lateral sclerosis). A Norwegian study published in the British Medical Journal Open in 2017 on the basis of national registers for the period 1977-2012, however, doubted this idea.
It is a rare disease (one birth in 2500), whose symptoms are extremely variable, which explains the frequent diagnosis of delay, despite the activism of patient associations. "Every year in October we organize a campaign in five European countries, including France, to raise public awareness and health professionals," he said. figaroDaniel Tanesse, president of the European Federation CMT. We are also talking about "CMT" because the classifications are refined to better distinguish the different symptomatic forms of the disease, both in terms of the type of damage to the nerves, the mode of genetic transfer or genetic abnormalities that are responsible. To date, more than 90 genes involved in CMT have been identified but six main types of CMT have been defined.
However, there are points that are common to all CMTs. These are diseases of genetic origin, so even if you do not see them immediately, they are there at birth. They affect the peripheral nerves, especially those of the arms and legs. Other diseases such as diabetes or nerve toxins can also lead to peripheral neuropathies.
Schematically, there are two types of peripheral nerves. The motor nerves, which start from the spinal cord (in the spine) to serve the muscle contraction, and the sensory nerves, which return to the spinal cord to bring back the sensory information (pressure, pain, temperature, position of the body). In CMT both types of nerves are affected, which explains the symptoms.
The disease begins with a decrease in sensitivity accompanied by muscle weakness in the feet, then gradually the calves and sometimes the thighs. After a few years, the hands and then the forearms can be reached in the same way. Sometimes the first symptoms appear on the hands. Mostly, CMTs start in childhood or in young adults.
As the muscles are less active, they will rapidly decrease in volume and retreat, which can lead to significant deformities, including feet: the arch will become wider and the toes become "claw" due to tendon retractions. The feet become insensitive and unstable, which disrupts walking, makes it difficult to climb stairs and stands upright. When hands are reached, fine movements can be complicated and malformations occur.
To make the diagnosis, measurements of the conduction of the nerve impulse (electroneuromyogram) are performed thanks to fine needles inserted into the tested muscle. Genetic tests also make it possible to determine the origin of the genetic abnormality in more than half of the cases.
Available from 2021
In October 2018, the French biotech Pharnext announced in a release the positive results of its phase 3 study with an original drug, PXT3003, on a type CMT (CMT1A). It is a combination, in low doses, of three molecules (baclofen, naltrexone and sorbitol) that are already used in other therapeutic indications.
On February 8, at 23es Days of the French Society of Peripheral Nerve, in the Institut Pasteur in Paris, the Pr Shahram Attarian, coordinator of the reference center for neuromuscular diseases at the Timone University Hospital in Marseille, has confirmed that the new application for a temporary use permit (ATU) in France is in progress.
"Of the 55 patients there was real efficiency in 14 of them, and some have stabilized, which is already a great success," he said, but the study has not yet been completed. "Thanks to the success of his Phase 3 study, the candidate drug from the French laboratory should be available from 2020-2021, according to the CMT France Association, and although tested on CMT1A, the most common form of our disease, it would also can be advantageous in other types of CMT. "Pr Attarian is optimistic: "It was about thirty years ago that we waited for treatment in a neuromuscular pathology, here is one."
Ethics repressed by innovative treatments
"There is so much hope, from families, but also from researchers, that we sometimes lose sight of the essential goal of improving the quality of life of patients."es days of the French Speaking Nerve Society do not come from anyone other than the Pr Odile Boespflug-Tanguy, chairman of the Scientific Council of AFM-Téléthon. The neuropedic surgeon is also coordinator of the reference center for leukodystrophies in the Robert Debré hospital (public assistance-Parisian hospitals) and Inserm Research Director. "I knew the time, there are about thirty years in which rare diseases do not interest anyone," she says, but now it has become a market that continues to grow for industrialists. medicine."
This is all the better, because thanks to the orphan drug that allows faster access to the medicines market and various tax benefits, research has finally got off the ground in rare diseases. But the Pr Boespflug-Tanguy remains cautious: "We know very well that there are genetic diseases for which we do not have satisfactory animal models, we have to think about what is ethically acceptable or not before we go further in the tests."