Riluzole an ALS Drug Offers New Hope for Acute SCI Patients

In a groundbreaking clinical trial led by a pharmacologist at the University of Houston, promising results have emerged in the use of the drug Riluzole for improving the functionality of individuals with acute spinal cord injuries (SCI). This study, accompanied by a pharmacokinetic sub-study, marks a significant step forward in the treatment of SCI, a condition that affects approximately 18,000 people in the United States each year. The findings, recently published in the Journal of Neurotrauma, offer hope for a new approach to treating acute SCI. 

Riluzole, originally approved by the U.S. Food and Drug Administration (FDA) in 1995 for the treatment of amyotrophic lateral sclerosis (ALS), has shown efficacy in improving outcomes for acute SCI patients when administered within 12 hours post-injury. The drug, traditionally used to manage seizures, operates by blocking specific sodium channels. However, this study has unveiled its potential as a neuroprotective agent, preserving nerve cells and aiding individuals in regaining lost functions after a spinal cord injury. 

Diana S-L Chow, the lead author of the study, holds the Paula & John J. Lovoi Sr. Endowed Professorship in Drug Discovery and Development and serves as the director of the Institute of Drug Education and Research at the UH College of Pharmacy. She emphasized that the positive results of the trial are indeed encouraging. Nevertheless, she cautioned that further investigations are required, primarily due to the relatively small number of participants in the trial, consisting of 32 patients with head and neck injuries. 

Chow explained, “The contribution of our investigation is to offer proof of concept for the drug discovery and development approach for SCI so that the scientific community may facilitate future treatments.” She noted that Riluzole can be prescribed for “off-label” use by physicians in clinical settings for purposes other than ALS, such as acute SCI, but it is not intended for chronic SCI patients until it receives FDA approval. 

The study’s implications go beyond its immediate findings, potentially influencing future dosing strategies, enhancing patient care, and improving therapeutic outcomes. The unique challenges posed by traumatic SCI’s acute and progressive nature, combined with the complexities of secondary injuries, significantly impact how the body processes drugs, a concept known as pharmacokinetics. To address this, the researchers developed a model to capture the dynamic behaviour of Riluzole and patient responses. 

This model included various motor scores in both upper and lower limbs, which are influenced by the complex pathophysiology of SCI and the progression of the condition following the injury. The study revealed that Riluzole could help reduce neuron cell damage in SCI patients, as evidenced by lower levels of a specific biomarker called phosphorylated neurofilament-heavy subunit (pNF-H) in those who received the treatment. 

Diana S-L Chow, an internationally recognized expert in the development and analysis of new drug formulations and drug-delivery systems, has a history of researching treatments for leukaemia, other cancers, and infections. She has also explored the stability and efficacy of medications used during space flights on the International Space Station.

One of the most significant outcomes of this study is the establishment of a link between short-term outcomes, such as pNF-H concentration, and long-term improvements in functional motor abilities. This connection suggests the possibility of predicting whether a patient will benefit from the treatment with long-term functional improvements early in the treatment process at the bedside through objective biomarker measurements. 

The study led by Diana S-L Chow at the University of Houston has opened new doors in the treatment of acute spinal cord injuries using Riluzole, a drug previously approved for ALS. While further research is necessary to solidify the findings, the study’s positive outcomes offer hope for individuals suffering from SCI and provide a foundation for future drug development and treatment strategies in this field. 

Journal Reference  

Diana Shu-Lian Chow et al, Riluzole in Spinal Cord Injury Study (RISCIS)–Pharmacokinetic (PK) Sub-Study: An Analysis of Pharmacokinetics, Pharmacodynamics, and Impact on Axonal Degradation of Riluzole in Patients with Traumatic Cervical Spinal Cord Injury Enrolled in the RISCIS Phase III Randomized Controlled Trial, Journal of Neurotrauma (2023). DOI: 10.1089/neu.2022.0499