Effect of sodium phenylbutyrate and taurursodiol on plasma concentrations of neuroinflammatory biomarkers in amyotrophic lateral sclerosis: results from the CENTAUR trial

Authors

Robert Bowser, Departments of Neurology and Translational Neuroscience, Barrow Neurological Institute, Phoenix, Arizona, USA Robert.Bowser@dignityhealth.org.Follow
Jiyan An, Departments of Neurology and Translational Neuroscience, Barrow Neurological Institute, Phoenix, Arizona, USA.
Lahar Mehta, Amylyx Pharmaceuticals, Inc, Cambridge, Massachusetts, USA.
Junliang Chen, Amylyx Pharmaceuticals, Inc, Cambridge, Massachusetts, USA.
Jamie Timmons, Amylyx Pharmaceuticals, Inc, Cambridge, Massachusetts, USA.
Merit Cudkowicz, Sean M. Healey and AMG Center for ALS & the Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Sabrina Paganoni, Sean M. Healey and AMG Center for ALS & the Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Document Type

Article

Abstract

BACKGROUND: An oral sodium phenylbutyrate and taurursodiol combination (PB and TURSO) significantly reduced functional decline in people living with amyotrophic lateral sclerosis (ALS) in the CENTAUR trial. Biomarkers linking clinical therapeutic effect with biological changes are of high interest in ALS. We performed analyses of neuroinflammatory biomarkers associated with ALS in the literature, including YKL-40 (also known as chitinase-3-like protein 1), chitinase 1 (CHIT1) and C reactive protein (CRP), in plasma samples collected in CENTAUR. METHODS: Log10-transformed plasma biomarker measurements were analysed using a linear mixed-effects model. Correlation between paired biomarker concentrations and ALS Functional Rating Scale-Revised (ALSFRS-R) total scores was assessed via Pearson correlation coefficients. RESULTS: By week 24, geometric least squares mean YKL-40 plasma concentration decreased by approximately 20% (p=0.008) and CRP by 30% (p=0.048) in the PB and TURSO versus placebo group. YKL-40 (r of -0.21; p<0.0001) and CRP (r of -0.19; p=0.0002) concentration correlated with ALSFRS-R total score. CHIT1 levels were not significantly different between groups. CONCLUSIONS: YKL-40 and CRP plasma levels were significantly reduced in participants with ALS receiving PB and TURSO in CENTAUR and correlated with disease progression. These findings suggest YKL-40 and CRP could be treatment-sensitive biomarkers in ALS, pending further confirmatory studies. TRIAL REGISTRATION NUMBER: https://clinicaltrials.gov/study/NCT03127514.

Keywords

ALS, MOTOR NEURON DISEASE, NEUROCHEMISTRY, NEUROMUSCULAR, RANDOMISED TRIALS

Publication Date

12-2-2023

Publication Title

Journal of neurology, neurosurgery, and psychiatry

E-ISSN

1468-330X

PubMed ID

38050066

Digital Object Identifier (DOI)

10.1136/jnnp-2023-332106

Recommended Citation

Bowser, Robert; An, Jiyan; Mehta, Lahar; Chen, Junliang; Timmons, Jamie; Cudkowicz, Merit; and Paganoni, Sabrina, "Effect of sodium phenylbutyrate and taurursodiol on plasma concentrations of neuroinflammatory biomarkers in amyotrophic lateral sclerosis: results from the CENTAUR trial" (2023). Translational Neuroscience. 2359.
https://scholar.barrowneuro.org/neurobiology/2359