Scientists have discovered a single genetic mutation in two families which caused people to develop a severe form of multiple sclerosis. The findings confirm that at least some forms the disease could be inherited.
So far, the prevailing view among scientists was that a combination of many genetic variations could increase the likelihood of falling sick with MS. However, none appeared to be more responsible than others in causing the disease.
"Many genes have been identified as having a role in MS, but their individual contribution is rather small. We were trying to identify a mutation of major effect that causes the disease within families", senior author Carles Vilarino-Guell explains.
The study, published in the journal Neuron, identified an alteration to the DNA that appears only in one in 1,000 MS patients, but leads to the development of the disease in two-thirds of the individuals who do have it.
One form of MS
Since 1993, a database of people with MS in Canada has been compiled thanks to a grant from the Multiple Sclerosis Society of Canada. It allowed researchers to get valuable information about patients' family history, medical history and demographics as well as to collect DNA samples.
The team, from the University of British Columbia, looked at some these samples from Canadian families with a strong history of MS – sequencing the genome to find genetic mutations specific to family members with MS.
In two families, they identified a mutation of gene NR1H3 in people affected by primary progressive MS. "In these two families, 70% of the people with the mutation we identified developed multiple sclerosis. This is the first time that we identify a mutation that actually causes the disease", says Vilarino-Guell.
Prevention and treatment
The mutation seems to lead to a rare type of MS. Indeed, the family members developed a rapidly progressive form of the disease, primary progressive MS which in total accounts for about 15% of all patients.
"This will help us look for new treatments, as we will be able to create a more accurate animal model thanks to genetically modified mice. We will be able to test different drugs on these animals, to see how they act on clinical phenotype manifestations that derive from the genetic mutation", Vilarino-Guell told IBTimes UK.
However, the discovery could also provide insight into the more common, fluctuating form of MS, known as 'relapsing-remitting', because in most cases, that disease gradually becomes progressive. The scientists also hope that this knowledge will help them develop better treatments against MS to tackle the causes of the disease and not its symptoms.
"We could even perhaps predict who may go on to develop MS and perhaps be able to do some treatment before MS hits the clinical stages", concludes co-author Dessa Sadovnick professor of medical genetics and neurology at the University of British Columbia.
What is Multiple Sclerosis?
Multiple Sclerosis (MS) affects about 100 000 people in the UK. MS targets the brain and the spinal chord, and is generally first diagnosed in individuals in their 20s and 30s. Woman are two to three times more affected than men.
Symptoms include fatigue, blurred vision, bladder problems, numbness, muscle stiffness, and problems with balance or working for long periods of time. There are different types of MS, with some people seeing their symptoms get gradually worse (primary progressive MS ) or alternating between moments of good health and relapses (relapsing-remitting MS). MS is lifelong condition that can sometimes cause serious disability, though in some cases it can be mild.
MS is an auto-immune disease, which means the problems stem from an abnormal immune system. In the case of MS, the immune system attacks the myelin sheath in the brain and spinal chord.
What causes the immune system to attack the myelin sheath is still unclear. Experts believe it is linked to a combination of genetic and environmental factors, such as smoking, lack of vitamin D or infections caused by the Epstein-Barr virus.