Investigators have reported the first single genetic mutation to cause multiple sclerosis (MS), according to a study published June 1, 2016 in the journal Neuron.
“Although we’ve had many families where MS seems to go from generation to generation, we've never been able to find a gene change that is specific to the cause of MS,” said one of the study’s authors A. Dessa Sadovnick, PhD, Professor of Medical Genetics in the Department of Medicine at the University of British Columbia (UBC), in Vancouver, Canada.
Dr. Sadovnick further explains her reasoning in this UBC video.
Only in recent years has MS been considered to have a genetic component; it was originally thought to be an autoimmune disease triggered by exposure to environmental agents, although genetic risk factors were later found to play a role in susceptibility. But this is the first discovery of a single genetic mutation to cause a particular form of MS.
The investigators found the mutation in two Canadian families that had several members diagnosed with an unusual form of MS that starts with a relapsing-remitting onset and rapidly becomes primary progressive MS. The scientists traced it to a pathogenic mutation in the NR1H3 gene.
“If you have this gene, chances are you will develop MS and rapidly deteriorate,” said study co-author Anthony Traboulsee, the MS Society of Canada Research Chair at UBC and Director of Vancouver Coastal Health’s MS and Neuromyelitis Optica Clinic.
Although only about 1 in 1,000 MS patients appears to have this mutation, its discovery helps reveal the biological pathway that leads to the rapidly progressive form, which accounts for about 15% of people with MS. The discovery could also provide insight into the more common relapsing-remitting form of MS, which in most cases gradually becomes progressive.
“This could give us a critical early window of opportunity to throw everything at the disease, to try to stop it or slow it,” Dr. Traboulsee added. “Until now, we didn’t have much basis for doing that.”
The NR1H3 gene produces the protein LXRA which, if turned off, could potentially inhibit the activation of the inflammatory cascade that leads to MS, the researchers predicted.
The investigators are now awaiting delivery of the first mice to be genetically engineered with this mutation, which will give them the opportunity to study the disease pathway as well as pave the way for possible therapeutic treatments for this currently untreatable progressive form of the disease.