A study of more than 22,000 people with multiple sclerosis has discovered the first genetic variant associated with faster disease progression that can rob patients of their mobility and independence over time.
Multiple sclerosis (MS) is the result of the immune system mistakenly attacking the brain and the spinal cord, resulting in symptom flares known as relapses as well as longer-term degeneration known as progression. Despite the development of effective treatments for relapses, some of which were pioneered at UCSF, none can reliably prevent the accumulation of disability.
The breakthrough findings, published in Nature on June 28, 2023, point to a genetic variant that increases the disease's severity and provide the first real progress in understanding and eventually fighting this aspect of MS.
"Inheriting this genetic variant from both parents accelerates the time to needing a walking aid by almost four years," said Sergio Baranzini, PhD, professor of neurology at UCSF and co-senior author of the study.
The work was the result of a large international collaboration of more than 70 institutions from around the world, led by researchers from UCSF and the University of Cambridge.
"Understanding how the variant exerts its effects on MS severity will hopefully pave the way to a new generation of treatments that are able to prevent disease progression," said Stephen Sawcer, a professor at Cambridge and the other co-senior author of the study.
A renewed focus on the nervous system
To address the mystery of MS severity, two large MS research consortia joined forces: The International Multiple Sclerosis Genetics Consortium (IMSGC) and The MultipleMS Consortium. This enabled MS researchers from around the world to pool the resources needed to begin to identify the genetic factors influencing MS outcomes.
Previous studies have shown that MS susceptibility, or risk, stems in large part from dysfunction in the immune system, and some of this dysfunction can be treated, slowing down the disease. But "these risk factors don't explain why, 10 years after diagnosis, some MS patients are in wheelchairs, while others continue to run marathons," explained Baranzini.
