A small clinical trial with a pharmacokinetic sub-study, led by a world-renowned pharmacologist at the University of Houston, has demonstrated promising efficacy of the drug riluzole in improving spinal cord function in people with acute cord injury (SCI) if the drug is used. Taken within 12 hours after injury.
Riluzole is among the first drugs to show efficacy for treating acute SCI, which affects an estimated 18,000 people in the United States each year. The US Food and Drug Administration (FDA) approved the drug in 1995 for the treatment of amyotrophic lateral sclerosis, also known as ALS or Lou Gehrig’s disease, with a daily oral dose of one 50-mg tablet twice a day. The same dosing regimen was used for this phase 2/3 multi-center clinical trial to re-administer the drug to SCI patients. The work is published Journal of Neurotrauma.
Riluzole is a drug that blocks certain sodium channels and is commonly used as an anticonvulsant. However, our studies demonstrate its neuroprotective potential to preserve nerve cells and help people recover their lost functions after spinal cord injury.”
Diana SL Chow, lead study author, Paula and John J. Lovoi Sr. Endowed Professor of Drug Discovery and Development and Director of the Institute of Drug Education and Research at the UH College of Pharmacy
Chow cautions that while the results of this study are positive, further investigation is needed due to the small number of participants involved in the trial – 32 patients with head and neck injuries were examined.
“The contribution of our investigation is to provide a proof-of-concept approach to drug discovery and development for SCI so that the scientific community can facilitate future treatments,” Chow said, adding that riluzole could be prescribed for “off-label” use. Doctors in clinical settings have different purposes, such as acute SCI. However, patients with chronic SCI cannot be used for purposes other than ALS prior to FDA approval.
“These findings have the potential to influence future dosing strategies, ultimately enhancing patient care and improving therapeutic outcomes,” he added.
The acute and progressive nature of traumatic SCI and the complications of secondary injury alter the pharmacokinetics of therapeutics, i.e., how the body processes drugs. For the clinical trial, researchers developed a model to capture the dynamic nature of drug behavior and patient response, including elbow flexor/extensor, wrist extensor, and upper limb finger flexor/abductor motor scores; Hip flexors, knee extensors, ankle dorsiflexors/plantar flexors and long leg extensors in the lower limb. All are affected by the complex pathophysiology of SCI and the progressive effects of the condition after injury.
“Our research emphasizes the need for a specific signal in the body that can tell us how well a treatment for spinal cord injury is working. In our study, we used a SCI-specific biomarker called phosphorylated neurofilament-heavy subunit (pNF-H). How Riluzole SCI show that it helps reduce neuron cell damage in . Our findings showed that patients who received the treatment had lower levels of pNF-H, confirming the drug’s positive effect on spinal cord injury,” Chou said.
Chow is an internationally recognized expert in the development and analysis of new drug formulations and drug-delivery systems for the treatment of leukemia, other cancers and infections. He also studied the stability and efficacy of drugs used in spaceflight on the International Space Station.
This recent study also established a link between short-term outcomes, such as pNF-H concentrations, and long-term improvements in functional motor ability. “This association suggests the potential for predicting whether a patient will benefit from treatment with long-term functional improvement early in the treatment process at the bedside through objective biomarker measurements,” he added.
Other members of the research team include Ashley Nguyen, a recent UH graduate and clinical pharmacologist at Johnson, Johnson & Johnson; Junghwa Park, PharmD and doctoral student; and Lei Wu, former research assistant professor and current associate director of clinical pharmacology at AbbVie Pharmaceutical Company; Elizabeth Gardiner Troupes, Houston Methodist Research Institute; James Shields Harrop, Thomas Jefferson University; James David Guest, University of Miami; Carl Michael Schmitt, UTHealth Houston; Bijhan Arabi, University of Maryland; Michael George Fehlings, University of Toronto; Maxwell Boakai, University of Louisville; and the late Robert Gerose Grossman, Houston Methodist Research Institute.
Material in Chow’s report is based on work supported by the US Army Medical Research Acquisition Activity, the Christopher and Dana Reeve Foundation, with supplemental funding from the UH College of Pharmacy’s Institute for Drug Education and Research (IDR).
Chow, D., etc. (2023). Riluzole in Spinal Cord Injury Study (RISCIS)-pharmacokinetic (PK) sub-study: analysis of pharmacokinetics, pharmacodynamics, and effects of riluzole on axonal degradation in patients with traumatic cervical spinal cord injury. Journal of Neurotrauma. doi.org/10.1089/neu.2022.0499.