United Press International - October 24, 2002
Michael Smith

In laboratory animal tests, the drug, called tat-NR2Bc, prevented up to 90 percent of the brain damage normally caused by stroke, neurosurgeon Michael Tymianski of the University of Toronto said. In addition, he told United Press International, tat-NR2Bc appears to cause few side effects.

The drug uses a tiny part of one of the genes of the human immunodeficiency virus to "trick" its way into brain cells, Tymianski said. When it reaches the cells, another part of the drug blocks self-destructive signals released as a result of the stroke, he said.

It targets proteins known as NMDA receptors that play a key role in the brain's internal communications. The receptors shift into overdrive when a stroke occurs, and send signals to toxic proteins tethered nearby to begin destroying the cell.

Blocking the activity of the NMDA receptors themselves has been tried, he said, but it failed because the receptors play a central role in the brain, so blocking them led to severe side effects such as coma.

Instead, Tymianski said, he and colleagues decided to "break the leash" that holds the toxic proteins close enough to receive signals from the receptors. The "leash" is another protein, called PSD-95. The researchers created inert proteins that tie up the PSD-95, preventing it from linking to the toxic proteins.

A stroke is caused by a blood clot that prevents oxygen from getting to part of the brain. That part of the brain then dies. One way of minimizing damage is to use so-called "clot-busting" drugs to remove the blockage, Tymianski said.

Unless those drugs are used within three hours of a stroke, however, they can cause brain hemorrhages -- a danger that limits their use, he said. Because of the danger, the clot-busting drugs are administered only after a careful examination has shown there actually has been a stroke.

Tat-NR2Bc seems to have no such dangers and potentially could be administered by paramedics within a few minutes of a suspected stroke, Tymianski said. He cautioned, however, that more testing is needed before the drug is used to treat humans.

"I don't want to raise false hopes," he said.

Nevertheless, he added, "Using a trick employed by one of mankind's greatest scourges, we were able to deliver a treatment for another of mankind's greatest scourges."

The approach is "exciting and innovative," said neurologist John Weiss of the University California, Irvine, but added it remains to be seen if the dramatic results in animals will translate to humans.

In animals, researchers can set up their experiments so they obtain the clearest possible result, Weiss told UPI, "but the human situation is so much more variable and complicated. If (Tymiansky's) idea is correct and if it works as he suggests ... they might have significant protection without deleterious side-effects."

Stroke is the third leading cause of death in North America.

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