Researchers have discovered a genetic mutation linked to the development of multiple sclerosis. A first which offers hope for new treatments.
The first genetic cause of multiple sclerosis has just been discovered. In study published this Wednesday in Neuron, a team from the University of British Columbia (Canada) describes this genetic mutation which would be directly linked to the development of this disease which attacks the nervous system.
“This result is crucial for our understanding of this pathology,” says Carles Vilariño-Güell, assistant professor in the department of medical genetics at the University of British Columbia and one of the study’s authors. We know very little about the biological mechanisms that contribute to the onset of the disease. This discovery paves the way for the development of new treatments that would fight against the root causes, and not just the symptoms. “
Multiple sclerosis is an autoimmune disease in which the immune system turns against myelin-producing cells, a membrane that surrounds neurons to protect them. Depending on the areas of the brain affected, patients may suffer from motor or sensory, visual, urinary or sexual disorders. At the onset of the disease, the symptoms disappear after a seizure, but in the long term a permanent handicap can set in. In France, around 80,000 people are affected. For almost 15% of them, multiple sclerosis has a hereditary component.
A rare mutation
But until now, scientists have failed to clearly identify genetic factors that could explain this familial predisposition. In contrast, the genetic mutation discovered by the Canadian team increases the risk of developing multiple sclerosis by 70%.
Researchers were able to make this pivotal discovery by drawing on genetic data from 2,000 Canadian families affected by this autoimmune disease. They particularly focused on families with at least 5 cases over 2 generations. Genomic analysis revealed a rare mutation in the gene called NR1H3 which leads to the production of a non-functional LXRA protein. A modification found subsequently in other families, and in particular in all patients suffering from a progressive form of multiple sclerosis.
A therapeutic avenue
Work in mice has shown that this same mutation induces neurological disorders, including a decrease in myelin production as in multiple sclerosis. “There is no doubt that this modification has biological consequences, and that the defective LXRA protein promotes the development of multiple sclerosis,” said Weihong Song, one of the study’s authors.
“It is important to note that even if this mutation is present only in one patient in 1,000, our genetic analysis has revealed other common variants in the same gene which are also risk factors. Thus, if the patients are not carriers of the rare mutation, treatments targeting this gene can help them, ”underlines Carles Vilariño-Güell, adding that drugs under development for other pathologies appear as promising candidates.
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