Background

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

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 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 ALSFRS-R (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 ALSFRS-R (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.