Urinary P75: a promising biomarker for amyotrophic lateral sclerosis.

Abstract:

Background: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal disease. The urinary neurotrophin receptor p75 extracellular domain (p75^ECD) has previously been reported as a potential disease biomarker for diagnosis, severity assessment and monitoring therapeutic response.

Methods: This study measured urinary p75^ECD using an enzyme-linked immunoassay and normalised the results against urinary creatinine. Participants were recruited via A Multicentre Biomarker Resource Strategy in ALS (AMBroSIA) programme. Study participants included 97 ALS patients, 24 of whom were studied longitudinally, and 27 healthy controls. The study focused on urinary p75^ECD and its potential association with different subtypes of ALS, change over time, disease progression, severity of symptoms and survival from symptom onset.

Results: Confirming previous findings, urinary p75^ECD levels were significantly higher in patients with ALS (median 6.78 ng/mg, 95% CI (5.12 to 9.23)) compared with controls (4.57 ng/mg, 95% CI (3.35 to 5.89)) at first study visit. There was a significant negative correlation between absolute change in the Revised ALS Functional Rating Scale score and p75^ECD levels (Spearman's rho=-0.371, p≤0.0004, 95% CI (-0.543 to -0.169)), indicating that an increase in the severity of motor neuron injury correlated with an increase in p75^ECD levels. There was a significant increase in p75^ECD between first and second samples in the same participants, indicating an increase in the level of this biomarker longitudinally during the disease course (moderate effect size of -0.3).

Conclusions: Urinary p75^ECD is a promising candidate as a biomarker, which increases with disease progression and has the potential to serve as a pharmacodynamic biomarker.