Evaluation of Phosphorylated Neurofilament Heavy Chain (pNF-H) as a Biomarker to Bridge Riluzole Treatment and Motor Outcomes in Patients with Acute Spinal Cord Injury (SCI)

Spinal Cord Injury (SCI) is a devastating acute neurodegenerative condition. Pharmacological therapies so far offer insignificant improvements in patients’ functional outcomes. Riluzole in Acute Spinal Cord Injury Study (RISCIS) Phase II/III trial (ClinicalTrials.gov- NCT01597518) was conducted to determine riluzole as a novel treatment for SCI by characterizing the relationship between pharmacokinetics of riluzole and motor outcomes in patients with SCI. However, since these clinical outcomes were measured at admission and six months after injury, it is quite challenging to correlate the 14-day riluzole exposure with its clinical response months after the therapy. To overcome the temporal gap between the treatment and motor outcomes, we performed further analysis using a novel biomarker, phosphorylated neurofilament heavy chain (pNF-H). As one of the structural proteins of neurons, elevated serum levels of pNF-H indicate the breakdown of axons over time, which implies the pathophysiological processes responsible for SCI disease progression. Our study aims to demonstrate the possibility of using pNF-H as a prognostic and predictive biomarker in patients with SCI by assessing the correlation between the improvement of motor scores in 6 months and the changes in pNF-H concentration after 14-day riluzole treatment.