Progressive multiple sclerosis: molecule that repairs the nervous system discovered

An Italian research published in Science Translational Medicine identifies bavisant as the first drug candidate capable of regenerating myelin and protecting neurons. Concrete hope for more than 15,000 people in Italy.

What progressive multiple sclerosis is and why it is so difficult to treat

Multiple sclerosis (MS)affects about 140,000 people in Italy and more than 2.8 million worldwide. Among its various forms, progressive multiple sclerosis is the most insidious: unlike the relapsing-remitting form--for which there are therapies that reduce relapses--progressive is characterized by continuous degeneration of nerve fibers and loss of myelin, the protective sheath that allows nerve signals to travel properly.

The result is a progressive loss of motor, visual and cognitive function that, to date, available drugs fail to halt. In Italy, it is estimated that between 15,000 and 20,000 people are living with this form of the disease, often with a high degree of dependence in daily activities.

The breakthrough: the bavisant and the BRAVEinMS

The breakthrough comes from the international BRAVEinMS consortium, launched in 2017 with funding from the International Progressive MS Alliance, and coordinated by the Università Vita-Salute San Raffaele and the IRCCS Ospedale San Raffaele di Milano, in collaboration with the Paris Brain Institute, the University of California San Francisco and the University of Münster.

From 1.500 molecules to one: how bavisant was found

The researchers built an unprecedented drug screening platform, combining:

• computational (in silico) analyses on large biological and pharmacological databases,
• human cell models derived from stem cells of patients,
• cultured brain tissue and experimental models of multiple sclerosis.

Based on an archive of more than 1.500 drugs already approved for use in humans (so-called repositioning drugs), the platform gradually narrowed the field: 1,500 molecules → 273 candidates → 32 compounds → 6 finalists → 1 molecule. The bavisant.

How bavisant acts on multiple sclerosis

Bavisant is a histamine H3 receptor antagonist, a drug with a safety profile already known in humans from studies conducted on sleep and wake disorders. In experimental models of multiple sclerosis-including human-mouse chimeras-it has demonstrated three key actions:

• Myelin regeneration:stimulates myelin-producing cells (oligodendrocytes) to repair damaged nerve fibers;
• Neuroprotection:protects neurons from oxidative degenerative damage;
• Anti-inflammatory effect:reduces the expression of genes involved in inflammation.

This dual action profile-- regeneration plus neuroprotection--distinguishes it from current MS drugs, which act primarily restraining the immune system without promoting repair of nerve tissue.

Why this discovery is important for patients

The fact that bavisant has already been tested in humans is a crucial advantage: the safety profile is known, which significantly shortens the time toward clinical trials. The BRAVEinMS consortium is now working on formulation optimization with the goal of initiating Phase 2 studies in humans relatively soon.

It should be emphasized that one is still in the preclinical research phase: the results observed in experimental models do not automatically guarantee the same efficacy in humans. However, the methodology adopted-which used 3D brain organoids derived from patient stem cells-makes the results significantly more predictive than in traditional animal models.

In addition to bavisant, the platform has identified 30 other potential therapeutic candidates, paving the way for a new generation of research on progressive SM.

Conclusions

The discovery of bavisant represents one of the most significant steps in recent years in progressive multiple sclerosis research. For the first time, a systematic approach based on human biological models has made it possible to identify a molecule capable of acting simultaneously on two of the central mechanisms of the disease: myelin regeneration and protection of neurons from degeneration. The fact that bavisant already has a known safety profile in humans potentially shortens the road to the clinic, making this discovery concretely hopeful, not just promising on paper.