In silico screening and preclinical validation identify bavisant as a therapeutic candidate for multiple sclerosis

Current treatments for multiple sclerosis (MS) are insufficient to delay the neurodegenerative process that is the main cause of disability progression in patients with MS. Therapeutics aimed at supporting myelin regeneration and neuroprotection are thus a major unmet medical need for the progressive forms of MS. To address this, we developed a strategy combining in silico screening of more than 1500 repurposed compounds with a validation pipeline of models, encompassing rodent and human in vitro assays as well as mouse models of demyelination/remyelination. From the initial library, 273 drugs were prioritized in silico on the basis of the predicted effects on myelination and neuroprotection, and among them, 160 were potentially nontoxic. We identified 32 molecules that exerted a promyelinating and a neuroprotective action on rodent and human oligodendroglia and neurons. Our data identified classes of compounds with potentially distinct mechanisms of action that may foster remyelination and neuroprotection. The therapeutic activity of one selected drug, the histamine receptor H3 antagonist bavisant, was further validated in mouse models of demyelination and axonal injury reproducing some key pathological features occurring in MS. Our in vivo studies demonstrated that bavisant promoted remyelination and neuroprotection when administered to LPC-treated, cuprizone-fed, or MOG-induced EAE mice, as well as in a human oligodendroglia chimeric mouse model of demyelination/remyelination. These findings provide proof-of-concept validation for bavisant as a candidate for neuroprotective clinical trials in MS.

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Publication Details

Journal
Science Translational Medicine
Published
2026-01-21
DOI
https://doi.org/10.1126/scitranslmed.ads0633
Citations
1
Primary Topic
Mast cells and histamine
Type
article
Field-Weighted Citation Impact
24.43
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article

In silico screening and preclinical validation identify bavisant as a therapeutic candidate for multiple sclerosis

Stefanie Albrecht, Stefania Olla, Nadjet Gacem, Cyrille Deboux et al.
1 citations
Science Translational Medicine
Mast cells and histamine
24.43
article

In silico screening and preclinical validation identify bavisant as a therapeutic candidate for multiple sclerosis

Stefanie Albrecht, Stefania Olla, Nadjet Gacem, Cyrille Deboux, M. Lévy, Norbert Goebels, Radmila Panic, Ivano Eberini, Beatriz García-Díaz, Alessia Formato, Jérémy Chazot, Farina Windener, S. Baranzini, Elif Nur Yılmaz, Svetlana Bezukladova, Alberto Bresciani, Elena Brambilla, Zipp Frauke, Jack P. Antel, Linda K Ottoboni, Anne Baron-Van Evercooren, Qiao-Ling Cui, Francesca Ruffini, Paola Panina-Bordignon, Karthik Soman, Raquel Guerrero González, Cristina Agresti, Brahim Nait-Oumesmar, Tala Karam
article en
1 citations

Abstract

Current treatments for multiple sclerosis (MS) are insufficient to delay the neurodegenerative process that is the main cause of disability progression in patients with MS. Therapeutics aimed at supporting myelin regeneration and neuroprotection are thus a major unmet medical need for the progressive forms of MS. To address this, we developed a strategy combining in silico screening of more than 1500 repurposed compounds with a validation pipeline of models, encompassing rodent and human in vitro assays as well as mouse models of demyelination/remyelination. From the initial library, 273 drugs were prioritized in silico on the basis of the predicted effects on myelination and neuroprotection, and among them, 160 were potentially nontoxic. We identified 32 molecules that exerted a promyelinating and a neuroprotective action on rodent and human oligodendroglia and neurons. Our data identified classes of compounds with potentially distinct mechanisms of action that may foster remyelination and neuroprotection. The therapeutic activity of one selected drug, the histamine receptor H3 antagonist bavisant, was further validated in mouse models of demyelination and axonal injury reproducing some key pathological features occurring in MS. Our in vivo studies demonstrated that bavisant promoted remyelination and neuroprotection when administered to LPC-treated, cuprizone-fed, or MOG-induced EAE mice, as well as in a human oligodendroglia chimeric mouse model of demyelination/remyelination. These findings provide proof-of-concept validation for bavisant as a candidate for neuroprotective clinical trials in MS.

Science Translational MedicineVol. 18(833)
Montreal Neurological Institute and Hospital (CA), Centre National de la Recherche Scientifique (FR), Vita-Salute San Raffaele University (IT), Inserm (FR), University of California, San Francisco (US), University of Milan (IT), Johannes Gutenberg University Mainz (DE), Istituto Superiore di Sanità (IT), Sorbonne Université (FR), University Medical Center of the Johannes Gutenberg University Mainz (DE), Assistance Publique – Hôpitaux de Paris (FR), University Hospital Münster (DE), Institute of Genetic and Biomedical Research (IT), IRBM Science Park (IT), Institut du Cerveau (FR), Heinrich Heine University Düsseldorf (DE)
Good health and well-being
Openalex Percentile: Top 2%
Mast cells and histamine
24.43
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