⚕️ A promising target against multiple sclerosis

A team from UNIGE and HUG has discovered a subgroup of immune cells particularly involved in the disease, opening the way to more precise treatments and avoiding certain side effects.

Multiple sclerosis, which affects about one in 500 people in Switzerland, is an autoimmune disease in which immune cells attack the central nervous system, leading to irreversible damage. Current treatments involve blocking the immune system to prevent it from attacking the body.

Although effective, these drugs can trigger potentially serious infections. A team from the University of Geneva (UNIGE) and the Geneva University Hospitals (HUG), in collaboration with the University of Pennsylvania, has identified, in recently diagnosed individuals, a subtype of immune cells that appear to be preferentially responsible for the progression of the disease. A treatment specifically targeting them could then effectively control the disease, while avoiding certain side effects. These results are published in the journal Annals of Neurology.



Multiple sclerosis is characterized by damage to the myelin, a membrane protecting neurons, essential for the transmission of nerve impulses. This results in motor, sensory, visual, and cognitive disorders that can lead to disability.

"For about twenty years, much progress has been made, both in early diagnosis and in the development of immunosuppressive drugs. These treatments inhibit the degradation process of the nervous system by limiting inflammatory flare-ups, which has led to a real improvement in the quality of life of affected individuals," says Patrice Lalive, professor in the Department of Clinical Neurosciences and the Department of Pathology and Immunology at the UNIGE Faculty of Medicine, and head of the Neuroimmunology Unit at HUG, who led this work. "However, these treatments indiscriminately destroy immune cells, opening the door to all kinds of infections and significant side effects."

This process could be a real opportunity to develop treatments.

A minority cell receptor

Patrice Lalive's team has been conducting research for over 10 years on a cell signaling pathway (a mechanism that allows cells to perceive their environment and communicate with each other), the c-Met/HGF pathway, involved in neuroinflammation. "Initial laboratory studies highlighted the role of this c-Met receptor in this process," details Patrice Lalive. "Here, we wanted to examine what actually happens in our patients."

The research team compared the white blood cells present in the blood and cerebrospinal fluid of about thirty people with recently diagnosed multiple sclerosis, who had not yet received any treatment, with those of people not suffering from the disease.

"We detected, in individuals with multiple sclerosis, the presence of lymphocytes expressing the c-Met receptor, which was absent in the 'control' individuals," explains Gautier Breville, physician-researcher in Prof. Lalive's team and first author of this work. "Moreover, these c-Met-expressing lymphocytes, which constitute only 5 to 6% of white blood cells in the cerebrospinal fluid, appeared particularly inflammatory and toxic, and passed more easily through the blood-brain barrier to attack the brain."

First steps towards targeted therapy

Thus, the abnormal pro-inflammatory mechanism of multiple sclerosis seems to favor the expression of c-Met in a small portion of lymphocytes. "This process could be a real opportunity to develop treatments capable of targeting only the c-Met-bearing lymphocytes, sparing the rest of the immune system necessary for our defense against infections. Would this be enough to limit the progression of the disease? That is what we now want to verify, by identifying molecules targeting c-Met," concludes Patrice Lalive.