A drug, Riluzole, which was approved by the Food and Drug Administration 28 years ago to treat amyotrophic lateral sclerosis (aka: ALS or Lou Gehrig’s Disease) was found by a team of researchers at the University of Houston to preserve nerve cells in patients facing permanent disability or worse from acute spinal cord injuries.
The research team’s hypothesis is that Riluzole, which blocks certain sodium channels and is commonly used as an anticonvulsant, could potentially, as lead study author Diana S-L Chow, Ph.D. said, exert a “neuroprotective potential to preserve nerve cells and help people regain some of their lost functions after spinal cord injury”.
Dr. Chow is the Paula & John J. Lovoi Sr. Endowed Professor in Drug Discovery and Development and director of the Institute of Drug Education and Research at the UH College of Pharmacy. She is an internationally recognized expert in the development and analyses of new drug formulations and drug-delivery systems for the treatment of leukemia, other cancers, and infection. She has also studied the stability and efficacy of medications used in space flights on the International Space Station.
The research team’s small clinical trial with a pharmacokinetic sub-study demonstrated that Riluzole could, in theory and as hypothesized, improve functionality in people with acute spinal cord injuries if the drug is taken within 12 hours post-injury.
Riluzole is among the first drugs to show efficacy for treating acute spinal cord injuries, which affects an estimated 18,000 people in the United States each year.
Dr. Chow cautions that while the results of this study are positive, further investigation is needed given the small number of participants involved in the trial—32 patients with head and neck injuries were enrolled.
“The contribution of our investigation is to offer the proof of concept for the drug discovery and development approach for acute spinal cord injuries so that the scientific community may facilitate future treatments,” said Dr. Chow.
Off-Label Use
Acute spinal cord injuries are true emergencies where patients present in the emergency rooms with spinal cord bruises, partial tears, or complete tears and are at high risk of permanent disability or death.
For that reason, it is important to mention that Riluzole can be prescribed for “off-label” use by physicians in clinical settings for different purposes, such as acute spinal cord injuries.
“These findings have the potential to influence future dosing strategies, ultimately enhancing patient care and improving therapeutic outcomes,” added Dr. Chow.
Study Methodology
Patients in the study were given a daily oral dose of one 50-milligram tablet twice a day. The same dosage regimen was used for this phase 2/3 multi-center clinical trial repurposing the drug for ACUTE SPINAL CORD INJURIES patients.
Given the acute and progressive nature of traumatic spinal cord injuries and the complexity of secondary injury, the research team also conducted a sub-study of the pharmacokinetics of therapeutics, namely, how the body processes a drug.
For that sub-study, the team developed a model to capture the dynamic nature of the drug’s behavior and patient response, including motor scores in elbow flexors/extensors, wrist extensors and finger flexors/abductors in the upper limbs; hip flexors, knee extensors, ankle dorsiflexors/plantar flexors, and a long toe extensor in the lower limbs.
All are influenced by the complex pathophysiology of acute spinal cord injuries and affects the patient healing.
“Our research underscores the need for a specific signal in the body that can tell us how well a treatment for spinal cord injuries works. In our study, we used an acute spinal cord injury-specific biomarker called phosphorylated neurofilament-heavy subunit (pNF-H) to show how Riluzole helps reduce neuron cell damage in acute spinal cord injuries. Our findings revealed that patients who received the treatment had lower levels of pNF-H, confirming the positive effect of the medication on spinal cord injuries,” said Dr. Chow.
The study also established a link between short-term outcomes, such as pNF-H concentration, and long-term improvements in functional motor abilities. “This connection suggests the feasibility of predicting if a patient will benefit from the treatment with long-term functional improvements early in the treatment process at the bedside through the objective biomarker measurement,” she added.
Other members of the research team include Ashley Nguyen, a recent UH graduate and clinical pharmacologist at Janssen, Johnson & Johnson; Junghwa Park, PharmD and doctoral student; and Lei Wu, previous research assistant professor and current associate director in clinical pharmacology of AbbVie pharmaceutical company; Elizabeth Gardiner Troups, Houston Methodist Research Institute; James Shields Harrop, Thomas Jefferson University; James David Guest, University of Miami; Karl Michael Schmitt, UTHealth Houston; Bizhan Aarabi, University of Maryland; Michael George Fehlings, University of Toronto; Maxwell Boakye, University of Louisville; and late Robert Geroge Grossman, Houston Methodist Research Institute.
The material in Dr. Chow’s report is based upon work supported by the U.S. Army Medical Research Acquisition Activity, the Christopher & Dana Reeve Foundation, with supplemental funding by the Institute for Drug Education and Research (IDER) of the UH College of Pharmacy.
The work, “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,” is published in the Journal of Neurotrauma.
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