Pubdate: Thursday, 28 May 1998

MEDICAL SCIENCE: HALTING THE IRREVERSIBLE

Judy Dempsey on the marijuana-derived drugs countering the effect of head
injury.

Israeli neurologists need go no further than their own country to recognise
the need for a drug to prevent the contamination of healthy brain cells
caused by serious head injuries.

Some 528 people in Israel were killed in road accidents last year and about
3,430 were seriously injured. Most deaths and injuries were caused by
damage to the head. Now, using substances derived from marijuana,
scientists may have found a solution.

When the brain is injured, trauma, strokes or even death do not occur
immediately. Brain cell molecules, tightly under control in a normally
functioning brain, start reacting wildly. Over a period of a few hours,
they rush from the damaged cells through narrow channels to other cells,
causing confusion and excitement. This process, known as neuronal cell
death, causes severe brain trauma.

There is also the danger of swelling. Under normal circumstances, water is
tightly controlled in the brain, operating like small blood vessels. But
following an injury, water enters the brain from outside. The cells cannot
cope; swelling occurs, often leading to strokes or death.

Finding a way to contain damaged cells - which would limit brain injury by
preventing neuronal cell death - is one project being undertaken by
Pharmos, a small biotechnology company based at the Kiryat Weizmann
scientific park close to Tel Aviv.

Haim Aviv, chairman of Pharmos as well as the Israel National Committee for
Biotechnology, says the company is developing a chemical compound,
Dexanabinol, which can protect healthy brain cells by blocking glutamate,
the neurotransmitter. Head trauma and strokes cause the release of
excessive glutamate, often resulting in irreversible damage to brain cells.

Pharmos has separated from marijuana properties for medical use that do not
induce psychotropic side affects associated with the drug. "With
Dexanabinol, we want to plug the receptor which sits at the entrance to the
channel of the cells," says Anat Biegon, a physiologist and vice-president
of research and development at Pharmos.

By blocking the channel, Dexanabinol, which has potent anti-oxidant and
anti-inflamatory properties, inhibits calcium influx in the primary neural
cells. This means it interferes with, or blocks, the cascade of biochemical
processes unleashed through an injury on the brain.

Pharmos started phase II trials for Dexanabinol in October 1996, involving
67 patients in six of Israel's neurotrauma centres. About 1,000 patients
will be involved in phase III, at a cost of $15m (£8.9m). According to
Sturza, the US medical investment analysts, Dexanabinol showed no serious
side effects when administered to healthy volunteers in a phase I trial.
The drug is administered through injection.

The market for such a drug is large, according to Jesup Lamont Securities,
US analysts. An estimated 500,000 strokes occur in the US each year while
worldwide more than 5m people suffer each year from stroke, head trauma or
other conditions associated with neuronal cell death.

Pharmos says it should soon be in a position when phase II trials are
complete to assess the level of neurological recovery.

Copyright the Financial Times Limited, 1998.

Checked-by: Richard Lake