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Genetic Variant Linked to Multiple Sclerosis Progression

For the first time, researchers identified a genetic variant associated with faster progression of multiple sclerosis.

Multiple sclerosis (MS) is an unpredictable disease of the central nervous system (CNS) that affects about one million Americans. Scientists still don’t know what causes the condition, which occurs when the immune system mistakenly attacks the protective myelin coating around the nerves.

A new study that appeared in the journal Nature may bring researchers closer to understanding the mechanisms involved in increasing disease severity.

For the first part of the new study, researchers used data from 12,584 people with MS to complete a genome-wide association study (GWAS). This research approach uses statistics to link genetic variants to particular traits. In the study, researchers analyzed the MS severity-related traits, such as the years it took for each individual to advance from diagnosis to a certain level of disability.

After sifting through more than 7 million genetic variants, the scientists identified one called rs149097173, linked with faster disease progression. The variant sits between two genes with no prior connection to MS, called DYSF and ZNF638. These genes help repair damaged cells, while one of them helps control viral infection.

The genetic variant was associated with accelerating time to requiring a walking aid by 3.7 years on average.

To confirm their findings, the researchers investigated the additional 9,805 additional cases of MS. Again, they found that those with two copies of the variant became disabled faster.

"These genes are normally active within the brain and spinal cord, rather than the immune system," says Adil Harroud, assistant professor of neurology at the Montreal Neurological Institute and lead author of the study. "Our findings suggest that resilience and repair in the nervous system determine the course of MS progression and that we should focus on these parts of human biology for better therapies."

While some MS patients will have a mild course of the disease with little impairment, in others, the condition steadily worsens and leads to disability over time. Most people with MS, however, will have short periods of symptoms followed by longer phases of inactivity, with partial or full recovery. In most severe cases, multiple sclerosis leads to partial or complete paralysis.

Early signs of multiple sclerosis often include:

  • Vision problems such as blurred or double vision
  • Muscle weakness and stiffness which can be accompanied by painful muscle spasms
  • Tingling, numbness, or pain in the arms, legs, trunk, or face
  • Clumsiness, especially difficulty keeping balance when walking
  • Bladder control problems
  • Intermittent or constant dizziness

Multiple sclerosis has no cure, but there are several FDA-approved disease modifying therapies (DMTs) that help to reduce the number and severity of relapses, as well as to slow down the damage caused by MS. A balanced diet, physical activity, and other healthy lifestyle choices can also help to manage the condition.

The study authors say their findings may help to develop new drugs to preserve the health of multiple sclerosis patients.

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