A rediscovered molecule opens a new path in progressive multiple sclerosis
In the nervous system of a person living with progressive multiple sclerosis the landscape slowly erodes, like a shoreline battered by an endless tide, axons fray, myelin peels away, signals dissolve into static, and medicine has long watched this retreat with few tools to offer in reply. Now a molecule once explored for the rhythms of sleep is being asked to play a far more ambitious score, helping nerve fibers rebuild their insulation while shielding neurons from decline, a double gesture that until now had remained more aspiration than reality.
Researchers at IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, leading an international network that stretches from Paris to San Francisco, from Münster and beyond, report in Science Translational Medicine that bavisant, an antagonist of the histamine H3 receptor, can coax myelin back onto damaged axons and temper the molecular storms that drive neurodegeneration, all within experimental models that closely mirror the human disease.
Drug repurposing and artificial intelligence in multiple sclerosis research
Progressive multiple sclerosis is the hardest face of the condition, a slow and relentless march affecting more than one million people worldwide, where inflammation gives way to structural collapse and therapies that calm the immune system arrive too late to stop the unraveling, what patients lose in movement, vision and memory current medicine cannot yet restore.
Against this backdrop the BRAVEinMS consortium set out to reverse the usual logic of drug discovery, not hunting blindly for new molecules but interrogating the pharmacological past, scanning more than fifteen hundred approved compounds through a layered pipeline that blends artificial intelligence, stem cell biology, brain tissue cultures and living models, a kind of wind tunnel in which only the strongest candidates survive. From this storm of data bavisant emerged, first as a computational signal, then as a cellular promise, and finally as a biological actor capable of speaking two languages at once, instructing oligodendrocytes to rebuild myelin while whispering protection to vulnerable neurons, reducing inflammatory gene expression and preserving axonal integrity in human–mouse chimeras and classical models of multiple sclerosis
From laboratory discovery to clinical translation in progressive MS
«For the first time we have shown that regeneration and protection can be achieved together through a systematic approach grounded in human biology,» explains Paola Panina-Bordignon, Professor of Experimental and Cell Biology at Vita-Salute San Raffaele University and senior co-author of the study, describing not only a candidate drug but a new grammar for translational research, faster, more predictive, and closer to the realities of people whose disease has long resisted intervention. The strength of the work lies as much in the platform as in the molecule, a knowledge graph called SPOKE guiding priorities, machine learning narrowing choices, and human induced pluripotent stem cells anchoring predictions to physiology, a choreography that allowed hundreds of possibilities to fall away until a single compound stood at center stage
Because bavisant is not born in a laboratory but rediscovered from an existing pharmacological lineage, the road ahead is shorter and safer, with known tolerability, reduced costs and timelines that matter when disability advances one synapse at a time.
A global alliance accelerating research in progressive multiple sclerosis
Behind this scientific journey stands an equally ambitious model of cooperation and funding promoted by the International Progressive MS Alliance, an unprecedented global collaboration that brings together the world’s leading multiple sclerosis associations, including the Italian Multiple Sclerosis Association and its Foundation, alongside researchers, clinicians, industry partners and people living with progressive forms of the disease, created to accelerate the development of effective treatments and improve quality of life, it was the Alliance that supported the birth of BRAVEinMS, transforming shared resources into a research infrastructure able to carry bold ideas from computation to preclinical reality and now toward the clinic.
Clinical translation remains the next horizon, with formulation and mechanism studies underway and the prospect of phase two trials now within sight, yet the broader legacy may be the platform itself, already yielding dozens of additional candidates and offering a template for regenerative strategies in other neurodegenerative diseases. As Gianvito Martino, Vice-Rector for Research and Third Mission at Vita-Salute San Raffaele University and Scientific Director of IRCCS Ospedale San Raffaele, reflects, this was a wager on collaboration and computation, on the idea that biology, engineering and global partnership could converge to change the fate of a disease once deemed inexorable, today that wager has produced not only a molecule, but a map.
