A novel synthetic compound with neuroprotective properties, dexanabinol is being developed by Pharmos as a drug to treat neurological damage associated with head injury, stroke and other neurological conditions. Pharmos has completed extensive pre-clinical work on dexanabinol, which demonstrated that the compound holds a unique position among putative neuroprotective agents, offering a combination of three mechanisms of action in one molecule – namely, blockade of glutamate neurotoxicity through non-competitive inhibition of the NMDA receptor channel, anti-inflammatory action through inhibition of TNF alpha and anti-oxidant activity in several animal models, including closed head injury, focal and global forebrain Ischemia and optic nerve crush. In all of these models, a single injection of dexanabinol given after the insult confers significant long term functional improvement and increased neuronal survival.
In a Phase I clinical trial conducted in more that 50 healthy volunteers, dexanabinol was proven to be safe and well tolerated. A Phase II multi-center, double blind, placebo-controlled, randomized trial of dexanabinol in severe head trauma (Glasgow coma scale of 4 to 8) is ongoing in Israel. Patients are followed over a six month period using standard clinical tests and scales such as Glasgow outcome scale (GOS) and disability-rating score (DRS).
Sixty-seven patients received one of two doses of dexanabinol or placebo and patients for the third dosage are currently being enrolled. Demographic analysis indicates that this patient population is representative of the characteristics describing the average severe head trauma patient: mostly young males, with motor vehicle accident as the primary cause of injury. The mortality rate in the study (eight deaths, 12.5%) is rather low compared to published records in severe head trauma clinical trials (19%-25%). An external safety committee is monitoring the study and there have been no safety concerns raised by the committee or the study physicians.