Trial of Sodium Phenylbutyrate–Taurursodiol for Amyotrophic Lateral Sclerosis
Open accessAbstract
BACKGROUND: Sodium phenylbutyrate and taurursodiol have been found to reduce neuronal death in experimental models. The efficacy and safety of a combination of the two compounds in persons with amyotrophic lateral sclerosis (ALS) are not known. METHODS: In this multicenter, randomized, double-blind trial, we enrolled participants with definite ALS who had had an onset of symptoms within the previous 18 months. Participants were randomly assigned in a 2:1 ratio to receive sodium phenylbutyrate-taurursodiol (3 g of sodium phenylbutyrate and 1 g of taurursodiol, administered once a day for 3 weeks and then twice a day) or placebo. The primary outcome was the rate of decline in the total score on the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R; range, 0 to 48, with higher scores indicating better function) through 24 weeks. Secondary outcomes were the rates of decline in isometric muscle strength, plasma phosphorylated axonal neurofilament H subunit levels, and the slow vital capacity; the time to death, tracheostomy, or permanent ventilation; and the time to death, tracheostomy, permanent ventilation, or hospitalization. RESULTS: A total of 177 persons with ALS were screened for eligibility, and 137 were randomly assigned to receive sodium phenylbutyrate-taurursodiol (89 participants) or placebo (48 participants). In a modified intention-to-treat analysis, the mean rate of change in the ALSFRS-R score was -1.24 points per month with the active drug and -1.66 points per month with placebo (difference, 0.42 points per month; 95% confidence interval, 0.03 to 0.81; P = 0.03). Secondary outcomes did not differ significantly between the two groups. Adverse events with the active drug were mainly gastrointestinal. CONCLUSIONS: Sodium phenylbutyrate-taurursodiol resulted in slower functional decline than placebo as measured by the ALSFRS-R score over a period of 24 weeks. Secondary outcomes were not significantly different between the two groups. Longer and larger trials are necessary to evaluate the efficacy and safety of sodium phenylbutyrate-taurursodiol in persons with ALS. (Funded by Amylyx Pharmaceuticals and others; CENTAUR ClinicalTrials.gov number, NCT03127514.).
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Oral combination of TUDCA and sodium phenylbutyrate (AMX0035) slows functional decline and prolongs overall survival in amyotrophic lateral sclerosis patients.
“Notably, an oral combination of TUDCA and sodium phenylbutyrate (AMX0035) is effective in slowing functional decline and prolonging the overall survival of ALS patients.400–402”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [401]
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- Authors
- Paganoni, S., Macklin, E. A., Hendrix, S., Berry, J. D., Elliott, M. A., Maiser, S., Karam, C., Caress, J. B., Owegi, M. A., Quick, A., Wymer, J., Goutman, S. A., Heitzman, D., Heiman-Patterson, T., Jackson, C. E., Quinn, C., Rothstein, J. D., Kasarskis, E. J., Katz, J., Jenkins, L., Ladha, S., Miller, T. M., Scelsa, S. N., Vu, T. H., Fournier, C. N., Glass, J. D., Johnson, K. M., Swenson, A., Goyal, N. A., Pattee, G. L., Andres, P. L., Babu, S., Chase, M., Dagostino, D., Dickson, S. P., Ellison, N., Hall, M., Hendrix, K., Kittle, G., McGovern, M., Ostrow, J., Pothier, L., Randall, R., Shefner, J. M., Sherman, A. V., Tustison, E., Vigneswaran, P., Walker, J., Yu, H., Chan, J., Wittes, J., Cohen, J., Klee, J., Leslie, K., Tanzi, R. E., Gilbert, W., Yeramian, P. D., Schoenfeld, D., & Cudkowicz, M. E.
- Affiliations
- Harvard University (US)
- Barrow Neurological Institute (US)
- From the Sean M. Healey and AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School (S.P., J.D.B., S.B., M.C., D.D., M.M., J.O., L.P., A.V.S., E.T., P.V., J. Walker, H.Y., R.E.T., M.E.C.), the Biostatistics Center, Massachusetts General Hospital, Harvard Medical School (E.A.M., J. Chan, D.S.), and Spaulding Rehabilitation Hospital, Harvard Medical School (S.P.), Boston, the University of Massachusetts Memorial Medical Center,...
- Mount Sinai Beth Israel (US)
- Ochsner Health System (US)
- University of Iowa (US)
- ORCID
- Paganoni, Sabrina
- Macklin, Eric A.
- Hendrix, Suzanne
- Berry, James D.
- Maiser, Samuel
- Karam, Chafic
- Caress, James B.
- Quick, Adam
- Wymer, James
- Goutman, Stephen A.
- Heiman-Patterson, Terry
- Jackson, Carlayne E.
- Quinn, Colin
- Rothstein, Jeffrey D.
- Kasarskis, Edward J.
- Ladha, Shafeeq
- Scelsa, Stephen N.
- Vu, Tuan H.
- Fournier, Christina N.
- Swenson, Andrea
- Goyal, Namita A.
- Pattee, Gary L.
- Babu, Suma
- Dickson, Samuel P.
- Pothier, Lindsay
- Randall, Rebecca
- Shefner, Jeremy M.
- Sherman, Alexander V.
- Yu, Hong
- Chan, James
- Cohen, Joshua
- Tanzi, Rudolph E.
- Schoenfeld, David
- Cudkowicz, Merit E.
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2020-09-03
- Volume
- 383
- Issue
- 10
- Pages
- 919-930
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC9134321
- OpenAlex
- W3082122716
- Cited by
- 536
- References
- 42
- Citations by year
- 2026: 49 · 2025: 74 · 2024: 124 · 2023: 131 · 2022: 98 · 2021: 47 · 2020: 11 · 2019: 2
- FWCI
- 31.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Amylyx Pharmaceuticals, Inc.
- The ALS Association
- ALS Finding ACure Foundation
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Genetics › Neurogenetic and Muscular Disorders Research
- Keywords
- amyotrophic lateral sclerosis, 4-phenylbutyric acid, combination therapy, functional decline, ALSFRS-R, neurofilament H, muscle strength, vital capacity, survival
- MeSH terms
- Aged, Amyotrophic Lateral Sclerosis, Double-Blind Method, Drug Combinations, Female, Humans, Male, Middle Aged, Phenylbutyrates, Severity of Illness Index, Taurochenodeoxycholic Acid, Treatment Outcome, Disease Progression, Intention to Treat Analysis
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