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
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This post is Copyright: Bowser, R., An, J., Mehta, L., Chen, J., Timmons, J., Cudkowicz, M., Paganoni, S. | June 17, 2024