Source: Boston Globe (MA) Contact: Website: Pubdate: Wed, 7 Oct 1998 Author: Larry Tye, Globe Staff


Test fuels hope for head injury victims

A drug modeled after a chemical found in marijuana could offer hope to hundreds of thousands of victims of severe head trauma, reducing the death rate and letting more people resume a normal life, according to a study being released today at an international conference in Seattle. The findings are drawing substantial interest, in part because head injuries are the leading cause of death among young people in the United States, and there are few if any treatments. And if these early results are substantiated, the new drug, called dexanabinol, would be the most medically useful treatment derived from the cannabis plant.

''It's hugely exciting,'' said Dr. Brian Andrews, who chairs the neurotrauma program of the American Association of Neurological Surgeons, which is meeting in Seattle and will hear today a presentation on the new drug. Dexanabinol, he added, appears to be just the sort of treatment ''that we have been looking for for years and years.'' Dr. William Beaver, professor emeritus of pharmacology at Georgetown University School of Medicine, is even more upbeat: ''This kind of treatment, if it works, would have tremendous impact on the treatment of neural injury and it could, of course, also be of value in something like strokes.'' The new drug also would be, ''beyond any doubt,'' the most medically significant use ever made of marijuana, said Beaver, who chaired a panel assembled last year by the National Institutes of Health to review possible medical uses of marijuana.

Scientists have been searching for 40 years for medicinal uses of the more than 400 chemicals in the marijuana plant, which is used to treat nausea and severe weight loss.

Dexanabinol is one in a series of compounds made in the laboratory and modeled after chemicals found in marijuana.

Dexanabinol's founder, Professor Raphael Mechoulam of Hebrew University in Jerusalem, sought to capture the neuroactive properties of the marijuana chemical, but not the psychoactive ones that induce a ''high.'' Mechoulam licensed dexanabinol to Pharmos Corp., an Israeli-based pharmaceutical firm, which has run two stages of clinic trials.

The first showed the drug was safe. The second, results of which are being released today, showed it could be remarkably effective.

The mortality rate among the 30 head trauma patients who took the drug was 10 percent, compared to 13.5 percent with 37 patients getting a placebo.

The incidence of low blood pressure, which can worsen a patient's condition, also was significantly reduced in the treated group (13 percent) versus placebos (38 percent). And, even more encouraging, the drug accelerated recovery and let 50 percent more patients resume a normal life six months after their injury.

How does dexanabinol work? The original trauma not only kills brain cells that were directly hit, but it also generates the release of chemicals that can kill or dangerously inflame surrounding cells.

Dexanabinol, which is given within six hours of the injury, protects the brain in three different ways, explains Anat Biegon, Pharmos' vice president for research and development. The drug mops up some of the dangerous chemicals, forms a protective barrier around at-risk brain cells, and limits intracranial inflammation.

Pharmos, which has just 45 employees, is looking for a bigger partner to help it launch a last phase of clinical trials involving as many as 900 patients worldwide.

Those tests, which could begin next year, would take about two years, predicted Pharmos chairman Haim Aviv. ''There are about 370,000 eligible patients with head trauma in the US, worldwide there are 700,000 to 800,000, and currently there is not a single drug there for them,'' Aviv added. ''We estimate there are 10,000 lives that could be saved by this drug ... and it could mean 37,000 more patients who could go back to a normal life.'' Dr. Christopher Ogilvy, director of cerebrovascular surgery at Massachusetts General Hospital, cautioned that ''a lot of chemical compounds used to treat head injury initially looked encouraging, but with rigorous testing they proved to be only