Clinical phase I trial with riluzole
Back to overview
After the initial injury created by the spinal cord trauma a series of secondary events further extend the size of the area affected by the injury, resulting in the end in a larger damage. One of these “secondary damage” mechanisms involves the influx on sodium within the neurons (see illustration) that results in a massive release of the neurotransmitter glutamate. Glutamate, which in normal quantities is essential for the proper function of the brain, becomes highly toxic in such amounts. This triggers then a massive death of neurons and associated cells (oligodendrocytes) finally resulting in a more severe functional damage.
Riluzole, a sodium channel–blocking drug, has the ability to block the sodium influx and therefore prevents the massive glutamate release (see illustration). A previous clinical trial focusing on the effect of riluzole on Amyotrophic Lateral Sclerosis (ALS) proved that the compound was able to slow down the symptoms and increase the chances of survival while having very little side effects. One side effect was an increase of lever enzymes, which was reversible with cessation of the riluzole therapy.
Additionally riluzole demonstrated significant neuroprotective effects in preclinical SCI models, leading the NACTN network to test it in spinal cord injured patients. 36 patients with acute SCI aged between 18 and 69 and with ASIA Impairment Scores (AIS) A to C were enrolled at 6 NACTN hospitals between April 2010 and June 2011.
50 mg of riluzole were administered every 12 hours within 12 hours of injury for 14 days. Subjects then received standard of care therapy. Neurological status was measured using ASIA scales during hospitalization, at 3 and at 6 months. Like on the ALS clinical trial beside a mild elevation of the liver enzyme in 2/3 of patients, no serious adverse events and medical complications were reported.
A recent presentation at the Society for Neuroscience meeting (New Orleans, USA) illustrated those findings. Since the number of patients enrolled was quite low, no conclusion can be taken yet on the efficacy of the treatment, but the ‘safety’ of the treatment led the NACTN network to plan a phase 2 study in which a larger number of patients will be enrolled.
Riluzole for the treatment of acute traumatic spinal cord injury: rationale for and design of the NACTN Phase I clinical trial. Fehlings MG, Wilson JR, Frankowski RF, Toups EG, Aarabi B, Harrop JS, Shaffrey CI, Harkema SJ, Guest JD, Tator CH, Burau KD, Johnson MW, Grossman RG. J Neurosurg Spine. 2012 Sep;17(1 Suppl): 151-6.