Genetic cause of multiple sclerosis discovered

Mutation causes autoimmune disease in 70 percent of its carriers

A gene mutation in GenNR1H3 triggers the onset of multiple sclerosis in 70 percent of its carriers. © Svisio / thinkstock
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Hope for MS patients: Researchers have first discovered a gene mutation that directly causes the onset of multiple sclerosis. Carriers of this mutation develop 70 percent of the neurological autoimmune disease. The exciting thing about it: although this mutation is also rare among MS patients, other changes in the same gene are not. The discovery of this trigger can therefore significantly advance the development of new therapies, as researchers report in the journal "Neuron".

"So far, little is known about the biological processes that lead to the onset of the disease, " says senior author Carles Vilariño-Güell of the University of British Columbia (UBC) in Vancouver. Physicians suspect that the permeability of the blood-brain barrier, but also the intestinal flora plays a role and that certain substances can aggravate the course.

It also seems clear that there is a genetic component of multiple sclerosis: in ten to fifteen percent of cases, the disease progresses very quickly and appears to be hereditary, but the gene variants discovered so far can only account for a very small part of the increased disease risk of the disease Declare the person concerned.

Gene mutation blocks tax protein

Now Vilariño-Güell and his colleagues could have achieved a breakthrough here. For their study, they evaluated data from a biobank of samples from 4, 400 people with multiple sclerosis and 8, 600 of their closest relatives. The researchers noticed a family that had five MS cases in two generations and were looking for potentially triggering gene mutations.

In fact, the scientists found what they were looking for: on a gene called NR1H3 they came across a short section whose direction was reversed. "This miss-sense mutation causes a loss of function of this gene, " explains co-author Weihong Song of the University of British Columbia. As a result, the regulation protein LXRA is no longer produced, which normally activates anti-inflammatory, immunoregulatory and myelin-protective genes. display

Multiple sclerosis: Myelin breakdown by the body's own immune cells disturbs the nerve conduction Marvin 101 / CC-by-sa 3.0

70 percent disease probability

After finding this gene mutation, researchers at the biobank specifically searched for additional cases and found a second family of trailed MS cases in which this gene had changed in the same way. From their data, they conclude that the carriers of this gene mutation have a 70 percent risk of contracting MS.

"The mutation somehow pushes these people to the brink of an abyss, " explains Vilari oG ell. This increases their susceptibility to environmental factors, which then cause the final outbreak. "Something has to be added that gives them the nudge that sets the disease process going."

Chance for new therapies

Although scientists estimate that only about one in every thousand MS patients has this mutation, their discovery could help to elucidate the biological mechanisms by which MS is triggered, Researchers have already identified other, more common changes in the same gene that are risk factors for progressive MS.

"Even if patients do not carry this rare mutation, we can use this genetic circuitry to develop therapies that will help other patients, " explains Vilari oG ell. "This discovery has tremendous potential for developing therapies that not only treat the symptoms, but their underlying causes."

Interestingly, in the context of other diseases, some agents are already being tested that target this gene circuit. "While we are still in the early stages and much work needs to be done, if we can reclassify some of these experimental specimens, it may be time to develop a new MS drug ", says Vilari oG ell. (Neuron, 2016; doi: 10.1016 / j.neuron.2016.04.039)

(Cell Press, University of British Columbia, 02.06.2016 - NPO)