Pharmos Compounds Demonstrate Neuroprotection 

Pharmos Compounds Demonstrate Neuroprotection 
Posted by FoM on November 19, 2001 at 11:03:35 PT
Press Release
Source: Pharmos Corporation
Pharmos Corporation (Nasdaq: PARS and Nasdaq Europe: PHRM) is presenting this week at the Society for Neuroscience Annual Meeting in San Diego three papers demonstrating the potential activity of its non-psychotropic dextrocannabinoids as agents to treat neuro-inflammatory disorders. Two of the papers present positive preclinical results in animal models for stroke and Parkinson's Disease. For stroke, PRS-211,095 was shown to induce significant dose-dependent functional recovery as well as reduction in brain infarct size following transient middle cerebral artery occlusion (MCAo) in rats. In a Parkinson's Disease mouse model, dexanabinol protected dopaminergic neurons of the central nervous system from MPTP toxicity. 
"The positive results we are obtaining with our compounds in animal models for various neurological indications support our decision to invest greater resources in this area of development. The sale of our ophthalmic business to Bausch & Lomb last month will help us advance promising early-stage programs into development and thereby strengthen our neurological pipeline," said Dr. George Fink, Vice President of Research at Pharmos.The third paper extends scientific understanding of the mechanisms of action of Pharmos' dextrocannabinoids. Collaborative studies with Drs. Marcus Schwaninger and Eric Juettler (Department of Neurology, University of Heidelberg) show for the first time that dexanabinol inhibits NF-kB, an important transcription factor in neuroinflammatory processes. Fink explained, "These results and data to be announced in the future demonstrate that our dextrocannabinoids affect cell signaling, particularly via gene regulation, cytokines and chemokines, and strengthen our ability to optimize our lead compounds and identify new clinical indications."Stroke Study Stroke was induced in rats by a 120-minute occlusion of the MCA, a standard animal model for focal ischemia. The animals were treated with a single intravenous injection of 0.5, 2.5, 5 or 10 mg/kg PRS-211,095 or vehicle alone at the end of MCAo. The neuroprotective efficacy of the compound was evaluated by brain infarct volume and by neurological outcome tested in the "staircase test," which measures a combination of sensory and motor skills similar to those impaired in humans who suffer a stroke. A dose-related improvement in performance in the staircase test was seen with PRS-211,095 (40-80% compared with vehicle alone, pParkinson's Disease Study MPTP is a toxin that induces a severe and irreversible Parkinson's Disease-like syndrome. In mice the agent causes a massive loss of the tyrosine hydroxylase (TH) immunoreactive (dopaminergic) cells in the substantia nigra, a key motor-control center of the brain that undergoes degeneration in Parkinson's Disease. Mice were injected with either MPTP toxin or saline four times at two-hour intervals. The MPTP-injected mice were treated with either dexanabinol (10, 20, 30 mg/kg) or its vehicle just before the first MPTP injection. One group of MPTP-injected mice was left untreated. After seven days, brain sections were analyzed for TH-positive cells by immunohistochemistry. Brain sections from mice treated with 20 mg/kg dexanabinol had 25-30% more TH-positive cells in the substantia nigra than sections from mice treated with vehicle alone (pDexanabinol Inhibition of NF-kB  Dexanabinol exerts anti-inflammatory effects, including the ability to inhibit expression of tumor necrosis factor (TNF) a. The gene expression of TNFa and various other mediators of inflammation are regulated by NF-kB, an essential transcription factor for many genes involved in the pathophysiology of brain damage, including cerebral ischemia and neural cell death. To investigate the effect of dexanabinol on NF-kB activation, U373 MG cells, an astrocytoma cell line, were transiently transfected with a reporter fusion gene that is under transcriptional control of NF-kB. Stimulation of NF-kB activity by TNFa, detected by luciferase assay, was inhibited by dexanabinol in a concentration-dependent manner. Western blot and gelshift assays were also employed and indicated dexanabinol inhibited NF-kB activation and nuclear translocation by its ability to block the TNFa - induced degradation of the NF-kB inhibitor, IkBa. In summary, the results show that dexanabinol is capable of inhibiting the activation of NF-kB, a mechanism by which dexanabinol could protect neuronal and other cells during neuroinflammation or ischemia.  Synthetic Non-Psychotropic Dextrocannabinoid Library  Pharmos is conducting both clinical and preclinical studies with neuroprotective compounds from its library of proprietary, synthetic, non-psychotropic dextrocannabinoids. The most advanced compound, dexanabinol, is in a pivotal Phase III clinical trial to treat traumatic brain injury (TBI). Another compound from the company's technology platform is in last-stage preclinical development for stroke. Beyond TBI and stroke, Pharmos believes its technology holds great promise in the development of safe and effective treatments for neuropathic pain, multiple sclerosis (MS) and other neurological and autoimmune conditions in which neuroinflammation is central to the pathology.Pharmos Corporation discovers and develops novel therapeutics to treat a range of neurological disorders, in particular those in which inflammation plays a role, such as traumatic brain injury and stroke. The Company has an extensive portfolio of drug candidates under development, as well as discovery, preclinical and clinical capabilities. Statements made in this press release related to operational expectations and projections of the Company are forward-looking and are made pursuant to the safe harbor provisions of the Securities Litigation Reform Act of 1995. Such statements involve risks and uncertainties which may cause results to differ materially from those set forth in these statements. Additional economic, competitive, governmental, technological, marketing and other factors identified in Pharmos' filings with the Securities and Exchange Commission could affect such results.Complete Title: Pharmos Compounds Demonstrate Neuroprotection in Stroke and Parkinson's Disease Models Newshawk: eyeknotSource: Pharmos CorporationPublished: November 12, 2001 Copyright: 2001 Pharmos CorporationWebsite: Related Articles & Web Site: Medical Marijuana Information Links Ingredient Helps Head Injuries May Reduce Brain Trauma Damage Marijuana: Good for The Brain
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Comment #5 posted by herbdoc215 on November 20, 2001 at 09:02:54 PT:
Race suppression spun into drug war
Mr. Johnson, That was a very insightful comment and one I have waited for years to become evident to more people. The 'Jim Crow' laws of the south have just been sanitized for the rest of the nation to embrace as the "Drug War", with selective perception and breaks given to folks from "Good Families"(i.e., white anglo-saxton,...) this has morphed into a suppression that is state-sponsored and harbored in most hearts of middle white Amerika who know full well that these horrble laws will never effect their families. My main problem is it seems that most black leaders today totally ignore this problem and have sold out for personal gain, those who speak truth being shot for standing up to a machine as bad as any in the world. 
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Comment #4 posted by E_Johnson on November 19, 2001 at 13:05:49 PT
African American women and marijuana
I was flipping around the TV during lunch and I saw this Judge Hackett show where there was this African American mother bringing her daughter to the Judge because her daughter was smoking six blunts a day.So they treated it like a drug crisis and had a cow and did whatever to make her shape up and put down the weed.But women suffer from autoimmune and chronic inflammatory diseases at a much higher rate than men, and African American women suffer from these diseases at a much higher rate than white women.And cannabinoids are increasingly being hailed for their potential value in treating autoimmune disorders such a rheumatoid arthritis:, politics, money and medicine, they're all mixed up here together. The problem is, these three African American women in this dramatic drug use conflict don't have access to science, they aren't going to come to, their doctors aren't going to let them know that MAYBE this young woman was smoking six blunts a day as a self-medication for lupus or arthritis or another autoimmune disorder that typically attacks African American women, something that is attacking her and dragging her down to where only marijuana can make her feel normal again.But instead of seeing it as a potential sign of a real medical problem, it's interpreted as a behavioral problem, one that can be solved by an application of the power of the law.It's one of the perversities of oppression, how oppressed people can be taught to oppress each other.
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Comment #3 posted by E_Johnson on November 19, 2001 at 12:23:48 PT
Didn't one already win a couple centuries ago?
Which do you think will reach market first in the USA?Like, um, dude... The people's farmacy has already spoken.
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Comment #2 posted by FoM on November 19, 2001 at 12:02:45 PT
The Big Bucks One
It sure will!
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Comment #1 posted by Ethan Russo MD on November 19, 2001 at 11:57:24 PT:
Dexanabinol is an interesting synthetic drug. It was previously called HU211, and is similar to a very potent cannabinoid agonist, HU210, except for one thing: it does not stimulate CB1 cannabinoid receptors.Dexanabinol can prove helpful in stroke and closed head injury protection. It will be extremely expensive.THC plus CBD (also known as cannabis) can achieve all the beneficial actions of dexanabinol, plus many more that it will not. If legalized, it could be very cheap. The side effect profile is well defined, and eminently manageable.Which do you think will reach market first in the USA?
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