Pharmos Reports Significant Brain Recovery in Stroke Models Using Dexanabinol - New Dexanabinol Analogs Seen as Powerful Neuroprotectants -
ISELIN, N.J., Nov. 7 /PRNewswire/ -- Pharmos Corporation (Nasdaq: PARS and Easdaq: PHRM) presented data this week at the Society for Neuroscience (SFN) Annual Meeting in New Orleans demonstrating significant improvements in long-term outcome, brain infarct size and mortality in rats subjected to experimental stroke and treated with dexanabinol. The SFN Annual Meeting serves as a premier arena for presenting new neuroscience research and attracts scientists and others worldwide.
Pharmos also announced that molecules in its library of novel second generation cannabinoids demonstrated significant anti-inflammatory and neuroprotective properties in various neurological tests of rats with brain ischemia induced by impairment of brain blood supply. ``This library of novel proprietary molecules is a valuable source of drug candidates that enhances our broad neurological and anti-inflammatory product pipeline for the treatment of neurological and cardiovascular diseases,'' said Dr. George Fink, Vice President of Research.
METHODOLOGY
Several independent experiments performed by Pharmos scientists demonstrate the superior performance of dexanabinol and two second generation cannabinoids, PRS 211,092 (092) and PRS 211,095 (095), when compared to standard compounds, MK-801 or FK 506, employed in experimental stroke models. Scientists induced stroke in rats by a 90 or 120 minute occlusion of the middle cerebral artery (MCAo), a standard animal model for focal ischemia. These animals were treated with one of the following: a single 5mg/kg dose of dexanabinol, 092, or 095; repeated doses of dexanabinol; single or multiple doses of MK-801; a single dose of FK 506; or vehicle only.
RESULTS
Mortality among the animals treated with single doses of 092 or 095 or with repeated doses of dexanabinol was 0%, while mortality among animals treated with a single dose of dexanabinol was 13%, all of which compared favorably to the mortality rate of 38% for FK 506, 0% and 38% for single or multiple doses of MK-801, respectively, and 27% for vehicle-treated animals. A single dose of dexanabinol, 092, 095, or FK 506 (known to be effective in moderating MCAo-induced brain ischemia) reduced the mean infarct size in the brain by 68%, 92%, 36%, and 35%, respectively, compared to infarct size in the control groups. Additionally, neuroprotection afforded by 092 and 095 was demonstrated by neurological deficit scores of 0.5 and 1.0, respectively, compared to 2.5 for vehicle-treated animals.
Sensorimotor function after induced brain ischemia was measured objectively by the staircase model. In this model, rats treated with dexanabinol or FK 506 showed a 50% - 60% improvement in neurological performance compared to the control group. ``This is an extremely positive result when coupled with the fact that dexanabinol's reduction in infarct size and mortality was superior to that of FK 506,'' said Dr. Fink. Among the conclusions made from these experiments is that dexanabinol, 092 and 095 demonstrated significant neuroprotective efficacy in reducing mortality and morbidity, and may prove beneficial in the treatment of human stroke.
NEUROPROTECTION AND ANTI-INFLAMMATORY LIBRARY
By employing rational drug design and combinatorial chemistry, Pharmos is developing a library of proprietary non-psychotic cannabinoids that is being screened (in vitro and in vivo) for activity in a variety of neuroprotective and anti-inflammatory tests. Categories for screening and selection include: NMDA binding activity, iNOS inhibition, COX-2 inhibition, TNF alpha - inhibition, binding to cannabinoid receptors, calcium influx into cells, and a variety of morphological and neurological measurements in animals.
``Our investments in combinatorial chemistry and high throughput screening technologies are bearing fruit in the selection of drug candidates for clinical development,'' said Dr. Haim Aviv, Chairman and CEO.
PHASE III STUDY PLANNED IN TRAUMATIC BRAIN INJURY
Pharmos will commence patient enrollment in a Phase III clinical trial of dexanabinol for traumatic brain injury in seven European countries and Israel upon receipt of approval by the appropriate regulatory authorities in each country. The Company recently hosted an investigators meeting attended by over 100 medical professionals comprising representatives from European trauma centers, the European Brain Injury Consortium, and others that are participating in the trial. Approximately 40 centers in Europe and Israel are expected to participate in this stage of the study. |
