Nav: Home

Scientists find genetic cause of multiple sclerosis

June 01, 2016

Scientists at the University of British Columbia and Vancouver Coastal Health have proven that multiple sclerosis (MS) can be caused by a single genetic mutation - a rare alteration in DNA that makes it very likely a person will develop the more devastating form of the neurological disease.

The mutation was found in two Canadian families that had several members diagnosed with a rapidly progressive type of MS, in which a person's symptoms steadily worsen and for which there is no effective treatment.

The discovery of this mutation should erase doubts that at least some forms of MS are inherited. The prevailing view has been that a combination of many genetic variations cause a slight increase in susceptibility. In the two families described in this study, two-thirds of the people with the mutation developed the disease.

"This mutation puts these people at the edge of a cliff, but something still has to give them the push to set the disease process in motion," said senior author Carles Vilarino-Guell, an assistant professor of medical genetics and a member of the Djavad Mowafaghian Centre for Brain Health.

Although only one in 1,000 MS patients appears to have this mutation, its discovery helps reveal the biological pathway that leads to the rapidly progressive form of the disease, accounting for about 15 per cent of people with MS. 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 findings, published today in the journal Neuron, could help in the search for therapies that act upon the gene itself or counteract the mutation's disease-causing effects. More immediately, screening for the mutation in high-risk individuals could enable earlier diagnosis and treatment before symptoms appear.

"If you have this gene, chances are you will develop MS and rapidly deteriorate," said co-author Dr. Anthony Traboulsee, the MS Society of Canada Research Chair at UBC and Director of Vancouver Coastal Health's MS and Neuromyelitis Optica Clinic. "This could give us a critical early window of opportunity to throw everything at the disease, to try to stop it or slow it. Until now, we didn't have much basis for doing that."
-end-
Background on MS and this discovery

Signal disruption: Multiple sclerosis results from the body's immune system attacking myelin, the fatty material that insulates neurons and enables rapid transmission of electrical signals. When myelin is damaged, communication between the brain and other parts of the body is disrupted, leading to vision problems, muscle weakness, difficulty with balance and coordination, and cognitive impairments. Canada has one of the highest rate of MS in the world, for reasons that elude scientists.

Defective protein: The MS-causing mutation discovered by UBC scientists was found on a gene called NR1H3. That gene produces a protein known as LXRA, which acts as an on-off switch on other genes. Some of those other genes stop the excessive inflammation that damages myelin or help create new myelin to repair the damage. A team led by Weihong Song, professor of psychiatry at UBC and the study's other senior author, found that the mutation of that gene - a substitution of just one nucleotide for another in the DNA - produces a defective LXRA protein that is unable to activate those other critical genes.

Early intervention: People with a family history of MS could be screened for this mutation, and if they carry it, could be candidates for early diagnostic imaging long before symptoms appear; or they could opt to increase their intake of Vitamin D (low levels of which have been associated with the disease). If someone diagnosed with relapsing-remitting MS were found to have this mutation, they might be candidates for earlier, more aggressive treatment to delay the onset of the progressive form of the disease.

A more realistic animal model: Vilarino-Guell and his collaborators are now awaiting delivery of the first mice to be genetically engineered with this mutation, enabling examination of the cascade of reactions that leads to MS. Currently, scientists simulate MS in mice by either injecting them with myelin, which triggers an immune response, or by feeding them a drug that destroys myelin directly. Neither one mimics how the disease originates in humans.

Thousands of samples: The families with this mutation had donated to a Canadian-wide collection of blood samples from people with MS, begun in 1993 by co-author A. Dessa Sadovnick, a UBC professor of medical genetics and neurology. The 20-year project, funded by the MS Society of Canada and the Multiple Sclerosis Scientific Research Foundation, has samples from 4,400 people with MS, plus 8,600 blood relatives - one of the largest such biobanks in the world.

University of British Columbia

Related Multiple Sclerosis Articles:

New biomarkers of multiple sclerosis pathogenesis
Multiple sclerosis (MS) is a chronic debilitating inflammatory disease targeting the brain.
Using telemedicine to treat multiple sclerosis
Multiple sclerosis (MS) clinicians face continued challenges in optimizing neurological care, especially for people with advanced MS living in medically underserved communities.
Improving symptom tracking in multiple sclerosis
With a recent two-year, $833,000 grant from the US Department of Defense, kinesiology professor Richard van Emmerik and colleagues at the University of Massachusetts Amherst hope to eventually help an estimated 1 million people worldwide living with progressive multiple sclerosis by creating an improved diagnostic test for this form of the disease, which is characterized by a steady decrease in nervous system function.
An antibody-based drug for multiple sclerosis
Inserm Unit U919, directed by Professor Denis Vivien has developed an antibody with potential therapeutic effects against multiple sclerosis.
Four new risk genes associated with multiple sclerosis discovered
Scientists of the Technical University of Munich and the Max Planck Institute of Psychiatry have identified four new risk genes that are altered in German patients with multiple sclerosis.
PET detects neuroinflammation in multiple sclerosis
The triggers of autoimmune inflammation in multiple sclerosis (MS) have eluded scientists for many years, but molecular imaging is bringing researchers closer to identifying them, while providing a means of evaluating next-generation therapies for MS, say researchers introducing a study at the 2016 Annual Meeting of the Society of Nuclear Medicine and Molecular Imaging.
Scientists find genetic cause of multiple sclerosis
Researchers have discovered a rare genetic mutation that makes it probable that a person will develop multiple sclerosis (MS).
ANKRD55: A new gene involved in Multiple Sclerosis is discovered
The Ikerbasque researcher Koen Vandenbroeck, who heads the Neurogenomiks laboratory which reports to the Achucarro centre and the UPV/EHU-University of the Basque Country, together with other national and international groups, has shown that a genetic variant in the 5q11 chromosome, which is associated with susceptibility to developing multiple sclerosis, greatly regulates a gene known as ANKRD55.
Children with and without multiple sclerosis have differences in gut bacteria
In a recent study, children with multiple sclerosis had differences in the abundance of specific gut bacteria than children without the disease.
Rituximab is superior to fingolimod for certain patients with multiple sclerosis
A new study indicates that rituximab is more effective than fingolimod for preventing relapses in patients with highly active multiple sclerosis switching from treatment with natalizumab.

Related Multiple Sclerosis Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Moving Forward
When the life you've built slips out of your grasp, you're often told it's best to move on. But is that true? Instead of forgetting the past, TED speakers describe how we can move forward with it. Guests include writers Nora McInerny and Suleika Jaouad, and human rights advocate Lindy Lou Isonhood.
Now Playing: Science for the People

#527 Honey I CRISPR'd the Kids
This week we're coming to you from Awesome Con in Washington, D.C. There, host Bethany Brookshire led a panel of three amazing guests to talk about the promise and perils of CRISPR, and what happens now that CRISPR babies have (maybe?) been born. Featuring science writer Tina Saey, molecular biologist Anne Simon, and bioethicist Alan Regenberg. A Nobel Prize winner argues banning CRISPR babies won’t work Geneticists push for a 5-year global ban on gene-edited babies A CRISPR spin-off causes unintended typos in DNA News of the first gene-edited babies ignited a firestorm The researcher who created CRISPR twins defends...