Hereditary Gene Mutation Could Potentially Lead to Multiple Sclerosis

Patients with mutations in the gene NR1H3 have a 70% chance of developing a progressive form of MS.

A recent study found that a gene mutation that can be directly linked to the development of multiple sclerosis (MS).

"This finding is critical for our understanding of MS," said study senior author Carles Vilariño-Güell, PhD. "Little is known about the biological processes that lead to the onset of the disease, and this discovery has massive amounts of potential for developing new treatments that tackle the underlying causes, not just the symptoms."

Approximately 10 to 15% of MS cases have a hereditary component. According to the study, published in Neuron, people who have this newly discovered genetic mutation have a 70% chance of developing MS.

Researcher analyzed materials from the Canadian Collaborative Project on Genetic Susceptibility to MS that contains genetic data for approximately 2000 families. Researchers included families who had 5 cases of MS over 2 generations and conducted exome sequencing to find coding mutations.

They discovered that all families with multiple cases of MS had the same mutation and also had a progressive form of MS.

"The mutation we found, in a gene called NR1H3, is a missense mutation that causes loss of function of its gene product, LXRA protein," said study senior author Weihong Song, MSc, PhD.

According to the study, LXRA controls transcriptional regulation of genes that control lipid homeostasis, inflammation, and innate immunity.

"There is clear evidence to support that this mutation has consequences in terms of biological function, and the defective LXRA protein leads to familial MS development," Dr Song said.

Even mice without this gene were said to have neurological problems.

"One thing that's important to note is that although this mutation is present in only about 1 in 1000 people with MS, by doing association analysis we've also found common variants in the same gene that are risk factors for progressive MS," Dr Vilariño-Güell said. "So even if patients don't have the rare mutation, treatments that target this pathway would likely be able to help them."

Researchers are hopeful that this discovery will let them develop cellular and animal models for MS that have not been available previously. They also said there are experimental drugs for atherosclerosis that target this pathway.

"These are still early days and there is a lot to test, but if we are able to repurpose some of these experimental drugs, it could shorten the time it takes to develop targeted MS treatments," Dr Vilariño-Güell concluded.