Data-driven identification of repurposable drugs for ALS

Abstract Amyotrophic lateral sclerosis (ALS) is a severe disease that causes thousands of deaths annually. Current treatments are either limited in effectiveness or not broadly applicable. To discover new options, we conducted a genetics-based screen to identify drugs that could be repurposed for ALS. We analyzed genome-wide data from over 150,000 samples ( n = 29,612 ALS patients and 122,656 controls) to assess the ability of FDA-approved drugs ( n = 1001) to restore disease-related gene expression. Our findings were validated using U.S. Medicare prescription claims data from 114,950 participants across diverse populations. The screen identified furosemide , a diuretic used for hypertension and heart failure, as a promising candidate for further research. Clinical trial simulations using public data further supported the beneficial effects of furosemide , and ex vivo experiments in mice suggest the drug may protect neurons by reducing hyperexcitability. Our data-driven, multidisciplinary approach has broad potential for repurposing drugs to treat neurodegenerative diseases.

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Publication Details

Journal
npj Digital Medicine
Published
2026-09-14
DOI
https://doi.org/10.1038/s41746-026-03225-w
Primary Topic
Amyotrophic Lateral Sclerosis Research
Type
article
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article

Data-driven identification of repurposable drugs for ALS

Miko Valori, J. Raphael Gibbs, Lilja Jansson, Claire Guissart et al.
npj Digital Medicine
Amyotrophic Lateral Sclerosis Research
article

Data-driven identification of repurposable drugs for ALS

Miko Valori, J. Raphael Gibbs, Lilja Jansson, Claire Guissart, Gabriele Mora, Lyle W. Ostrow, Michael Sendtner, Travis Dunckley, Alexis Brice, Francesco Landi, Ruth M. Pfeiffer, Serge Lumbroso, R. Bowser, David J. Stone, Daniele Cusi, Huaibin Cai, Stefan M. Pulst, Liisa Myllykangas, Sara Sáez-Atiénzar, Kévin Mouzat, Carsten Drepper, Hannu Laaksovirta, Christopher B. Brady, Janine Kirby, John Ravits, Robert H. Baloh, Daniel J. MacGowan, Stephen A. Goutman, Ekaterina Rogaeva, Eva Feldman, Summer Gibson, Mary Kay Floeter, John Cooper-Knock, Zachary Simmons, Glenn Gerhard, James Broach, Pentti J. Tienari, John Hardy, Jonathan D. Glass, Isabelle Le Ber, Stuart Pickering-Brown, Lorne Zinman, Matthew B. Harms, Philip Van Damme, Maurizio Grassano, William Camu, Ruth Chia, Vivian E. Drory, Katie C. Sidle, Pamela J. Shaw, Luis A. Rojas-Colón, Bryan J. Traynor, Adriano Chiò, Sonja W. Scholz, Juan C. Troncoso, Terry D. Heiman-Patterson, Nicholas J. Maragakis, Jinhui Ding, Gerald M. Gaitos, Richard W. Orrell, Erika Salvi, Alan E. Renton, John Q. Trojanowski, Jeffrey D. Rothstein, Vivianna M. Van Deerlin, John E. Landers, Wim Robberecht, Ludo Van Den Bosch, Erik P. Pioro, Pietro Fratta
article en

Abstract

Abstract Amyotrophic lateral sclerosis (ALS) is a severe disease that causes thousands of deaths annually. Current treatments are either limited in effectiveness or not broadly applicable. To discover new options, we conducted a genetics-based screen to identify drugs that could be repurposed for ALS. We analyzed genome-wide data from over 150,000 samples ( n = 29,612 ALS patients and 122,656 controls) to assess the ability of FDA-approved drugs ( n = 1001) to restore disease-related gene expression. Our findings were validated using U.S. Medicare prescription claims data from 114,950 participants across diverse populations. The screen identified furosemide , a diuretic used for hypertension and heart failure, as a promising candidate for further research. Clinical trial simulations using public data further supported the beneficial effects of furosemide , and ex vivo experiments in mice suggest the drug may protect neurons by reducing hyperexcitability. Our data-driven, multidisciplinary approach has broad potential for repurposing drugs to treat neurodegenerative diseases.

npj Digital Medicine
Università Cattolica del Sacro Cuore (IT), Cedars-Sinai Medical Center (US), Translational Genomics Research Institute (US), National Institutes of Health (US), Cleveland Clinic (US), Sunnybrook Health Science Centre (CA), Barrow Neurological Institute (US), University of Helsinki (FI), NewYork–Presbyterian Hospital (US), University of British Columbia (CA), Johns Hopkins University (US), Emory University (US), Inserm (FR), University of Massachusetts Chan Medical School (US), University of Toronto (CA), Université de Montpellier (FR), Cornell University (US), University of Utah (US), University of Würzburg (DE), University of Michigan (US), Toronto Western Hospital (CA), Tel Aviv Sourasky Medical Center (IL), Johns Hopkins Medicine (US), Sobell House (GB), Helsinki University Hospital (FI), VA Boston Healthcare System (US), Health Sciences Centre (CA), Amyotrophic Lateral Sclerosis Association (US), Agostino Gemelli University Polyclinic (IT), The Ohio State University Wexner Medical Center (US), University Medical Center (US), University of Manchester (GB), University of California San Diego (US), Azienda Ospedaliera Citta' della Salute e della Scienza di Torino (IT), Rodin Therapeutics (United States) (US), Centre Hospitalier Universitaire de Nîmes (FR), National Institute of Neurological Disorders and Stroke (US), Hôpital Gui de Chauliac (FR), Novartis (United States) (US), Universitätsklinikum Würzburg (DE), Institute for Neurosciences of Montpellier (FR), National Institute on Aging (US), National Cancer Institute (US), National Center for Advancing Translational Sciences (US), Institut du Cerveau (FR), VIB-KU Leuven Center for Brain & Disease Research (BE), Fondazione IRCCS Istituto Neurologico Carlo Besta (IT), Hospital District of Helsinki and Uusimaa (FI), Institute of Cognitive Sciences and Technologies (IT), Bio4Dreams (Italy) (IT), Division of Cancer Epidemiology and Genetics, Djavad Mowafaghian Centre for Brain Health (CA), University College London (GB), University of Turin (IT), Columbia University (US), University of Pennsylvania (US), Penn State Milton S. Hershey Medical Center (US), Temple University (US), University of Sheffield (GB), Icahn School of Medicine at Mount Sinai (US), KU Leuven (BE)
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