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

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.

• Authors: Stephanie R Shepheard, Vassilios Karnaros, Beben Benyamin, David W Schultz, Megan Dubowsky, Joanne Wuu, Tim Chataway, Andrea Malaspina, Michael Benatar, Mary-Louise Rogers
• Journal: European journal of neurology (Eur J Neurol) Vol. 29 Issue 4 Pg. 990-999 (04 2022) ISSN: 1468-1331 [Electronic] England
• PMID: 34967083 (Publication Type: Journal Article, Observational Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 European Academy of Neurology.

Chemical References

• Biomarkers
• Neopterin

Topics

• Amyotrophic Lateral Sclerosis (diagnosis)
• Biomarkers
• Disease Progression
• Humans
• Neopterin
• Prognosis