Trial of sodium phenylbutyrate-taurursodiol for amyotrophic lateral sclerosis

Sabrina Paganoni, Eric A. Macklin, Suzanne Hendrix, James D. Berry, Michael A. Elliott, Samuel Maiser, Chafic Karam, James B. Caress, Margaret A. Owegi, Adam Quick, James Wymer, Stephen A. Goutman, Daragh Heitzman, Terry Heiman-Patterson, Carlayne E. Jackson, Colin Quinn, Jeffrey D. Rothstein, Edward J. Kasarskis, Jonathan Katz, Liberty JenkinsShafeeq Ladha, Timothy M. Miller, Stephen N. Scelsa, Tuan H. Vu, Christina N. Fournier, Jonathan D. Glass, Kristin M. Johnson, Andrea Swenson, Namita A. Goyal, Gary L. Pattee, Patricia L. Andres, Suma Babu, Marianne Chase, Derek Dagostino, Samuel P. Dickson, Noel Ellison, Meghan Hall, Kent Hendrix, Gale Kittle, Michelle McGovern, Joseph Ostrow, Lindsay Pothier, Rebecca Randall, Jeremy M. Shefner, Alexander V. Sherman, Eric Tustison, Prasha Vigneswaran, Jason Walker, Hong Yu, James Chan, Janet Wittes, Joshua Cohen, Justin Klee, Kent Leslie, Rudolph E. Tanzi, Walter Gilbert, Patrick D. Yeramian, David Schoenfeld, Merit E. Cudkowicz

Research output: Contribution to journalArticlepeer-review

275 Scopus citations


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 number, NCT03127514.).

Original languageEnglish
Pages (from-to)919-930
Number of pages12
JournalNew England Journal of Medicine
Issue number10
StatePublished - 3 Sep 2020


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