Riluzole, a drug approved already for treating ALS, has been shown in a Phase I safety trial, yes, to be safe. These results, published last week in the Journal of Neurotrauma
, also showed the drug may help patients regain some motor function if they get it within 12 hours of injury.
The Phase 1 trial was the first operated by the North American Clinical Trials Network (NACTN)
, a group of 10 major center neurosurgery departments created by the Reeve Foundation to speed the testing of potential therapies for SCI in a coordinated, multicenter setting. NACTN has been supported by the US Army Medical Research and Materiel Command, which recently announced its continued support for the Network and the riluzole trial with a $2 million dollar contract
The results are promising, though modest. A second larger trial has been set.
Robert Grossman, M.D., professor of neurosurgery at The Methodist Hospital Neurological Institute in Houston and principal investigator of NACTN, was PI on the safety study. Said he: “We don’t want to over-advertise the Phase I results, or to claim too much. “But there were no serious adverse events in the first study and the data are encouraging; we are eager to move to a larger trial.”
The Phase II/III trial – called RISCIS, for Riluzole in Spinal Cord Injury Study – will include 350 patients with cervical injuries, the group that seems to benefit most from the drug, at as many as 20 clinical centers. This trial is being led by Michael Fehlings, M.D., Ph.D., professor of neurosurgery and medical director of the Krembil Neuroscience Center at the University of Toronto.
Said Fehlings, “In the Phase I riluzole group, 50 percent of patients with complete motor and sensory injuries – ASIA A patients converted [improved to ASIA B, or incomplete] – compared to only 25 percent in a group not treated but matched with NACTN’s large registry of controls.” The Phase I trial included 36 patients with traumatic acute spinal cord injury from C4 to T12. Most patients were male (83 percent) and had a cervical injury (78 percent).
One big advantage to riluzole is that it can be administered enterally (tablet form); patients take it every 12 hours for 14 days.
The drug is thought to work by blocking sodium channels, which in turn prevents the stimulation of glutamate receptors; excess glutamate can be toxic to nerves. The drug is “ideally suited as an early-phase treatment in spinal cord injury,” said Fehlings.
The Phase I patients that seemed to improve most were ASIA Bs, those with some spared sensory or motor function. Fehlings speculated that riluzole seems most neuroprotective in cervical patients probably for reasons of anatomy and the fact that these injuries tend to be "low energy" and therefore offer more opportunity for protection.
The RISCIS trial, set to begin this summer, may take two years to enroll all patients. The study hopes to learn how a particular dosage of riluzole correlates to motor function outcome. “All medications have a window for dose response,” said Grossman. “We don’t know what that is for this drug. But one of the advantages of NACTN is that we have a pharmacology group, in Houston, that can help us establish the relationship between the blood-level of riluzole and clinical outcome.”
The RISCIS study is being funded collaboratively by Department of Defense support for NACTN and by AOSpine, an international education and research society of 6,000 spine doctors that has funded studies related to musculoskeletal science, such as arthritis, spinal cancer, spinal deformity and trauma.
AOSpine was founded in 1958 by four neurosurgeons from Switzerland, using royalties from surgical tool innovations to create a foundation – now with a sizeable endowment.
Ultimately, said Grossman, riluzole is not likely to be a “magic bullet” type treatment. “The real hope is that the drug will provide some neuroprotection, and then if we can add a regenerative strategy to that – anti-Nogo [nerve growth promotion] or even stem cells, we can enhance recovery. The less severe the injury, the better the recovery. That may seem obvious, but we hope riluzole can prevent some damage so that a regenerative treatment can work better.”