Urinary neopterin: A novel biomarker of disease progression in amyotrophic lateral sclerosis

Stephanie R. Shepheard, Vassilios Karnaros, Beben Benyamin, David W. Schultz, Megan Dubowsky, Joanne Wuu, Tim Chataway, Andrea Malaspina, Michael Benatar, Mary Louise Rogers

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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 (p75ECD). Methods: This was an observational study including 21 healthy controls and 46 people with ALS, 29 of whom were sampled longitudinally. Neopterin and p75ECD were measured using enzyme-linked immunoassays. Baseline and longitudinal changes in clinical measures, neopterin and urinary p75ECD 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 p75ECD results from 22 ALS patients with a further 24 ALS patients, baseline urinary p75ECD 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 p75ECD 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 p75ECD 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.

Original languageEnglish (US)
Pages (from-to)990-999
Number of pages10
JournalEuropean Journal of Neurology
Volume29
Issue number4
DOIs
StatePublished - Apr 2022
Externally publishedYes

Keywords

  • ALS
  • biomarker
  • disease progression
  • pharmacodynamic
  • proinflammatory

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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