12 genes at the root of multiple sclerosis identified

Summary: 12 genes associated with familial multiple sclerosis have been identified. The findings provide a molecular rationale for the chronic inflammation, demyelination and neurodegeneration associated with MS. Identifying new genetic targets could help with the development of novel treatments to prevent multiple sclerosis in those with a genetic risk.

Source: University of British Columbia

An international team of researchers led by the University of British Columbia has made a scientific advance they hope will lead to the development of preventative treatments for multiple sclerosis (MS).

In a study published today in PLOS Genetics, researchers found mutations in 12 genes believed to be largely responsible for the onset of MS in families with multiple members diagnosed with the disease.

“These genes are like a lighthouse illuminating where the root cause of MS is,” said lead author Carles Vilariño-Güell, assistant professor in the UBC faculty of medicine’s department of medical genetics and a Michael Smith Scholar.

MS is a disease that affects the central nervous system, in which cells from the immune system attack and damage the nerve cells’ protective sheath. The disease often results in disability and can have a significant impact on quality of life.

For the study, researchers sequenced all known genes in three or more MS patients from 34 families and examined the genetic variants in family members both affected by and unaffected by MS. By looking at the genes of 132 patients, they identified 12 genetic mutations that can lead to an overactive autoimmune system that attacks myelin, the insulating layer around nerves in the brain and spinal cord.

Of people diagnosed with MS, only 13 per cent are believed to have a genetic form of the disease, but those presenting the mutations identified in this new study were estimated to have an up to 85 per cent chance of developing MS in their lifetime.

Vilariño-Güell aims to develop cellular and animal models with the identified mutations to mimic the biological processes responsible for the onset of MS in patients, with the goal of eventually developing preventative treatments for the disease.

This is a DNA strand

The researchers hope the findings will one day lead to personalized treatments for MS patients and preventative strategies for those at greater risk of developing the disease. The image is in the public domain.

“We have treatments that address the symptoms of MS, but not the causes. People with MS take drugs that reduce the attacks, but the disease still progresses,” said Vilariño-Güell. “Now, with knowledge of these mutations, which suggest a common biological process that leads to increased inflammation in MS families, we can try to address the root causes.”

The researchers hope the findings will one day lead to personalized treatments for MS patients and preventative strategies for those at greater risk of developing the disease.

Funding: This study was supported in part by the Canada Research Chair program, the Michael Smith Foundation for Health Research, the Canadian Institutes of Health Research, the Vancouver Coastal Health Research Institute, the Milan & Maureen Ilich Foundation and the Vancouver Foundation.

About this neuroscience research article

Source:
University of British Columbia
Media Contacts:
Cheryl Rossi – University of British Columbia
Image Source:
The image is in the public domain.

Original Research: Open access
“Exome sequencing in multiple sclerosis families identifies 12 candidate genes and nominates biological pathways for the genesis of disease”. Vilariño-Güell et al.
PLOS Genetics. doi:10.1371/journal.pgen.1008180

Abstract

Exome sequencing in multiple sclerosis families identifies 12 candidate genes and nominates biological pathways for the genesis of disease

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system characterized by myelin loss and neuronal dysfunction. Although the majority of patients do not present familial aggregation, Mendelian forms have been described. We performed whole-exome sequencing analysis in 132 patients from 34 multi-incident families, which nominated likely pathogenic variants for MS in 12 genes of the innate immune system that regulate the transcription and activation of inflammatory mediators. Rare missense or nonsense variants were identified in genes of the fibrinolysis and complement pathways (PLAU, MASP1, C2), inflammasome assembly (NLRP12), Wnt signaling (UBR2, CTNNA3, NFATC2, RNF213), nuclear receptor complexes (NCOA3), and cation channels and exchangers (KCNG4, SLC24A6, SLC8B1). These genes suggest a disruption of interconnected immunological and pro-inflammatory pathways as the initial event in the pathophysiology of familial MS, and provide the molecular and biological rationale for the chronic inflammation, demyelination and neurodegeneration observed in MS patients.

Feel free to share this Neuroscience News.
Join our Newsletter
I agree to have my personal information transferred to AWeber for Neuroscience Newsletter ( more information )
Sign up to receive the latest neuroscience headlines and summaries sent to your email daily from NeuroscienceNews.com
We hate spam and only use your email to contact you about newsletters. We do not sell email addresses. You can cancel your subscription any time.
No more articles