Genetics is a new key in the treatment of multiple sclerosis – 06/29/2023 – Equilíbrio

Scientists identify genetic variant that accelerates the progression of multiple sclerosis. In contrast to medications that only treat symptoms, the discovery makes room for the development of new treatments, attacking the progressive nature of the disease.

An international scientific team has discovered the first genetic variant linked to the progression of the condition. To this end, data from about 22,000 patients were analyzed in a study covering the entire human genome, using statistical techniques to meticulously associate genetic variants with specific characteristics.

Researchers at the University of California, San Francisco (USCF) and Cambridge, UK, concluded that inheriting this variant from both parents speeds up, on average, nearly four years the time when walking support devices will be needed, in comparison with other multiple sclerosis patients.

The variant in question is located between two genes, one involved in repairing damaged cells and the other in controlling viral infections. Both are active in the brain and spinal cord.

“This is compelling evidence of how the degree of severity of multiple sclerosis is profoundly influenced by the brain’s ability to resist attacks on the immune system,” says Stephen Sawcer, professor of neurology at the University of Cambridge and co-author of the study published in the journal Nature. .

A researcher on the disease since the mid-1990s, he considers the identification of the variant a major breakthrough in research: “I’ve been working on this for several decades, and this is the most important thing I’ve ever discovered.”

Wide range of symptoms

Multiple sclerosis is an autoimmune disease, in which the immune system mistakenly attacks the brain and spinal cord, damaging myelin, the fatty structure that surrounds and insulates nerve fibers. This compromises the nervous system’s ability to transmit electrical signals.

Flare-ups of the condition have diverse symptoms, including numbness and tingling of the limbs, face or trunk, mood swings, memory lapses, pain, fatigue, blindness and paralysis. The severity and frequency of these attacks varies greatly from case to case.

“Some patients do not show any symptoms, sometimes it is only found post-mortem that they had multiple sclerosis”, says Sawcer. “They can have very mild symptoms that afflict them for a while and then they don’t come back for a long time. Last week I saw a patient I had seen for the first time 15 years ago, who had been perfectly fine in the meantime, and was now coming back with a new episode. Or the symptoms could be very severe: the woman in the next bed was very incapacitated, she could barely feed herself.”

All previously identified multiple sclerosis-related genetic variants influenced the degree of risk of developing the disease. The current one is the first to indicate where the patient should be placed on the spectrum of symptom severity: important data for the development of treatments.

Attacking disease progression

Currently, there are several drugs on the market to treat the symptoms of multiple sclerosis, but none that addresses its global advance. Thus, some patients get worse faster than others.

“All of the drugs developed to control flare-ups are immunomodulatory, which is consistent with the genetics of the more than 200 variants associated with multiple sclerosis risk,” says one of the study’s lead authors, UCSF professor of neurology Sergio Baranzini. “The genetics of disease severity now suggest that the central nervous system should be the target of this new class of therapy.”

Sawcer emphasizes that the fact that patients who inherited two copies of the newly identified variant needed walking aids sooner does not mean that one can make personalized predictions about the course of the condition. To do so, it will be necessary to identify many other variants in studies that encompass the entire human genome.

Still, now that it is possible to pinpoint a specific variant associated with disease progression and how it involves genes normally active in the brain, it is much more likely that pharmaceutical companies will invest in developing a drug that targets progression.

“The main unmet need of patients with multiple sclerosis is a medication, a treatment for the progressive aspect of the disease”, reinforces the neurologist. “And the prospects for achieving that have changed radically today.”