A Genetic Basis for MS

Canada has the world’s highest rate of multiple sclerosis (MS) and over the past few decades, the University of British Columbia (UBC) in Vancouver has amassed a great deal of clinical information and biological samples (thanks to the MS Society of Canada and the Canadian Collaborative Project on Genetic Susceptibility to MS). The resources represented an excellent research opportunity that Carles Vilariño-Güell, Assistant Professor in the Department of Medical Genetics at UBC, could not ignore.

“Our study clearly showed that in some families with many individuals diagnosed with MS, there is a strong genetic component likely responsible for the onset of the disease. To try to identify the cause of the disease we sequenced the entire coding DNA in several of those families,” says Vilariño-Güell.

The sequencing analysis showed that a mutation on the NR1H3 gene was the common familial link, and further investigation suggested that pathogenic mutations in NR1H3 cause primary progressive MS (1). Moreover, the researchers believe that common variants in the same gene may lead to an increased susceptibility to the disease.

Now, the UBC team hopes to use the findings to develop more efficient therapies for MS, and preliminary work is already underway. “We can now create mouse models that are more likely to represent the processes that are disrupted in patients, which will be extremely useful in studying the biological problems caused by these mutations, as well as the development of new treatments,” says Vilariño-Güell.

The researchers are also using the clinical resources to gain more insight into the disease’s mechanisms. “We believe NR1H3 is just one of many genes to be discovered in MS families, thus we’re studying additional MS families to identify others, which will provide more pieces of the puzzle to better understand MS,” concludes Vilariño-Güell.