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

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

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)990-999
Number of pages10
JournalEuropean Journal of Neurology
Volume29
Issue number4
Early online date29 Dec 2021
DOIs
Publication statusPublished - Apr 2022

Keywords

  • ALS
  • biomarker
  • disease progression
  • pharmacodynamic
  • proinflammatory

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