An international research team has discovered the first genetic variant related to the progression of multiple sclerosis (MS).
The group, led by scientists from the University of California, San Francisco (UCSF), and the University of Cambridge in the United Kingdom, analyzed data from roughly 22,000 MS patients in a genome-wide association study, which uses statistics to carefully link genetic variants to particular traits. Their results were published in the journal Nature on Wednesday.
On average, the researchers point out in the study, inheriting this variant from both parents speeds up the time to needing a walking stick by almost four years as compared to MS patients who didn't inherit the variant from mother and father.
The genetic variant in question sits between two genes, one of which is involved in repairing damaged cells and the other in controlling viral infections. Both of these genes are active within the brain and spiral cord.
"That's convincing evidence that whether you do well or badly with MS is profoundly influenced by how well your brain can cope with the immune system attacks" that occur as part of MS, says Stephen Sawcer, a professor of neurology at the University of Cambridge and co-senior author of the study published in Nature.
Sawcer wrote his PhD thesis on multiple scleroris in the mid-1990s and has studied the disease extensively since then. The identification of the genetic variant described in the Nature study is a big advancement in MS research.
"I've worked on this now for several decades and this is the most important thing I have ever discovered," Sawcer told DW.
What is multiple sclerosis?
To understand what makes the discovery of this genetic variant so exceptional — and different from all previous discoveries in MS research — it's necessary to take a closer look at multiple sclerosis. It's an autoimmune disease in which the immune system mistakenly attacks the brain and the spinal cord.
These attacks damage the myelin, the fatty substance that surrounds and insulates nerve fibers, which disrupts the nervous system's ability to transmit signals.
These relapses, as the attacks are called, can result in a wide variety of symptoms including numbness, tingling, mood changes, memory problems, pain, fatigue, blindness or paralysis.
How severely MS patients are affected and how often relapses occur varies greatly.
"Some patients have no symptoms, sometimes you find it post-mortem and we never even knew they had MS," said Sawcer, who also treats MS patients as a doctor. "They can have very mild symptoms that trouble them for a while and then don't come back for a long time. I had a woman the other week who I first saw 15 years ago and now she was back with a new episode, and she'd been completely well in between. Or symptoms can be very serious — the woman in the bed next to her was very disabled, barely able to feed herself."
Why this genetic variant is important in MS research
All of the MS-related genetic variants previously discovered helped determine someone's risk of developing MS. This recent one is the first to give an idea of where patients might fall on the spectrum of disease severity. That's important when it comes to the development of treatments.
So far, there are several drugs on the market to treat the symptoms of MS relapses, but none to treat the general progression of the disease, which means some patients will see their condition deteriorate faster than others.
"All drugs developed to control relapses are immunomodulatory, which matches the genetics of the more than 200 variants associated with MS risk," Sergio Baranzini, a professor of neurology at UCSF and co-senior author of the study, wrote in an email to DW. "The genetics of disease severity now suggests that the central nervous system should be the target of this new class of therapeutics."
Prospects of getting a new MS treatment 'radically transformed'
The fact that the group of patients who inherited two copies of the newly discovered genetic variant needed a walking aid in a shorter space of time does not mean, however, that the variant can be used to make personalized predictions for individual patients. Sawcer says many more genetic variants need to be identified before this is possible, so more genome-wide association studies are necessary.
Still, Sawcer says that now that they can point to a specific variant associated with MS progression and know that it involves genes normally active within the brain, pharmaceutical companies are much more likely to start investing money in the development of a drug that targets progression.
"The number one unmet need for MS patients is a drug, a treatment for the progressive aspect of the disease," Sawcer said. "And the prospects of getting that radically transformed today."
