X-Message-Number: 12173
Date: Thu, 22 Jul 1999 16:34:18 -0400
From: Jan Coetzee <>
Subject: Limit Stroke Damage

New Compound May Help Limit Stroke Damage - Study

By Maggie Fox, Health and Science Correspondent

WASHINGTON (Reuters) - An experimental new drug might help limit the
damage caused by
stroke by preventing the immune system from spilling over and damaging
delicate nerve cells,
researchers said Thursday.

The drug has only been tested in mice. But the testing supports the idea
that inflammation after a
stroke brings about a cascade of cell death in which brain cells are
destroyed over several hours
or even days.

The compound, known by the experimental name of TP20, is made by
Massachusetts-based Avant Immunotherapeutics Inc. (Nasdaq:AVAN - news).

Dr. David Pinsky, a professor of medicine at Columbia University in New
York who helped test
the drug, said it works in two ways -- first by stopping one part of the
immune system, known as
complement, from activating.

Complement is a series of proteins that punch holes in cells, destroying
them. It is meant to act
against invaders but ''it is a little bit indiscriminate once it is
activated,'' Pinsky said.

But second, the compound was modified by Avant, Pinsky added.

``It was coated with a very special sugar which interferes with adhesion
receptors -- those are
basically sticky molecules on the surface of cells. It prevents white
blood cells and perhaps
platelets from coming into the area and gumming up the blood vessels.''

Each year about 550,000 Americans suffer a stroke.

There are two kinds -- ischemic and hemorrhagic. In an ischemic stroke a
blood clot cuts off
blood to the brain. Some brain cells die instantly.

But other brain damage develops slowly, sometimes over weeks, as cells
die. Drugs that can stop
this could help prevent the paralysis, speech problems and other brain
dysfunction that can
cripple stroke victims.

The brain is protected from the immune system by a system known as the
blood-brain barrier.
When a stroke occurs, Pinsky said, the immune cells -- and complement --
can spill over and
damage delicate neurons.

But Pinsky's team found something else.

``One of the new findings was the fact that nerve cells, when they are
subjected to ischemia,
when they are in an area where blood flow is diminished, they express
this complement protein
on their surface,'' Pinsky said.

``They bristle with it. It's all over them. That's what triggers this

Pinsky said it is too soon to tell how quickly TP20 would have to be
given after a stroke to do
any good. He said it is a long way from being tested in human beings.

This ``window of opportunity'' is important.

The only drug on the market to limit damage after a stroke is
Genentech's clotbuster Activase,
which is also known as tissue plasminogen activator or tPA, and it must
be given within three
hours to work.

Many other companies are working on drugs, however.

Abbott Laboratories (NYSE:ABT - news) Inc. says its clot-busting drug,
pro-urokinase, can be used six hours after a stroke. It is expected to
seek approval this year.

Interneuron Pharmaceuticals Inc. (Nasdaq:IPIC - news) says CerAxon,
known generically as
citicoline, is in Phase III clinical trials in people, the last stage
before seeking approval.

Parke-Davis, a division of Warner-Lambert Co., is testing an
experimental drug known as

Ancrod, made by Knoll Pharmaceuticals, lowers the level of fibrinogen in
the blood, which is
necessary for clotting.

Creative BioMolecules Inc. says its drug OP-1 appears to help the brain
compensate for areas
damaged by stroke, and works up to 72 hours after a stroke.

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