Urinary neopterin: A novel biomarker of disease progression in amyotrophic lateral sclerosis. (11th January 2022)

• Record Type: Journal Article
• Authors: Shepheard, Stephanie R.; Karnaros, Vassilios; Benyamin, Beben; Schultz, David W.; Dubowsky, Megan; Wuu, Joanne; Chataway, Tim; Malaspina, Andrea; Benatar, Michael; Rogers, Mary‐Louise
• Is Part Of: European journal of neurology. Volume 29:Number 4(2022)
• Page Start: 990
• Page End: 999
• Publication Date: 2022-01-11
• Subjects: ALS -- biomarker -- disease progression -- pharmacodynamic -- proinflammatory; Neurology -- Periodicals; Nervous system -- Diseases -- Periodicals; 616.8
• DOI: 10.1111/ene.15237
• Languages: English
• ISSNs: 1351-5101

Abstract

Abstract: Background and purpose: The aim was to evaluate urinary neopterin, a marker of pro‐inflammatory state, as a potential biomarker of disease prognosis and progression in amyotrophic lateral sclerosis (ALS); and to compare its utility to urinary neurotrophin receptor p75 extracellular domain (p75 ECD ). Methods: This was an observational study including 21 healthy controls and 46 people with ALS, 29 of whom were sampled longitudinally. Neopterin and p75 ECD were measured using enzyme‐linked immunoassays. Baseline and longitudinal changes in clinical measures, neopterin and urinary p75 ECD were examined, and prognostic utility was explored by survival analysis. Results: At baseline, urinary neopterin was higher in ALS compared to controls (181.7 ± 78.9 μmol/mol creatinine vs. 120.4 ± 60.8 μmol/mol creatinine, p = 0.002, Welch's t test) and correlated with the Revised ALS Functional Rating Scale ( r = −0.36, p = 0.01). Combining previously published urinary p75 ECD results from 22 ALS patients with a further 24 ALS patients, baseline urinary p75 ECD was also higher compared to healthy controls (6.0 ± 2.7 vs. 3.2 ± 1.0 ng/mg creatinine, p < 0.0001) and correlated with the Revised ALS Functional Rating Scale ( r = −0.36, p = 0.01). Urinary neopterin and p75 ECD correlated with each other at baseline ( r = 0.38, p = 0.009). In longitudinal analysis, urinary neopterin increased on average (±SE) by 6.8 ± 1.1 µmol/mol creatinine per month ( p < 0.0001) and p75 ECD by 0.19 ± 0.02 ng/mg creatinine per month ( p < 0.0001) from diagnosis in 29 ALS patients. Conclusion: Urinary neopterin holds promise as marker of disease progression in ALS and is worthy of future evaluation for its potential to predict response to anti‐inflammatory therapies. Abstract : The pro‐inflammatory marker urinary neopterin was investigated as a disease progression biomarker for amyotrophic lateral sclerosis. It was also compared to urinary p75 extracellular domain (p75 ECD ). Urinary neopterin and p75 ECD progressively increased from diagnosis. Urinary neopterin might serve as a biomarker of an underlying pro‐inflammatory state in amyotrophic lateral sclerosis.