New Method Holds Promise For Treating Brain Injuries
An injury to the brain can be devastating. When brain cells die,
whether from head trauma, stroke or disease, a substance called
glutamate floods the surrounding areas, overloading the cells in its
path and setting off a chain reaction that damages whole swathes of
tissue. Glutamate is always present in the brain, where it carries
nerve impulses across the gaps between cells. But when this chemical is
released by damaged or dying brain cells, the result is a flood that
overexcites nearby cells and kills them...
A new method for ridding the brain of excess glutamate has been
developed at the Weizmann Institute of Science. This method takes a
completely new approach to the problem, compared with previous attempts
based on drugs that must enter the brain to prevent the deleterious
action of glutamate. Many drugs, however, can't cross the blood-brain
barrier into the brain, while other promising treatments have proved
ineffective in clinical trials. Prof. Vivian Teichberg, of the
Institute's Neurobiology Department, working together with Prof. Yoram
Shapira and Dr. Alexander Zlotnik of the Soroka Medical Center and Ben
Gurion University of the Negev, has shown that in rats, an enzyme in
the blood can be activated to "mop up" toxic glutamate spills in the
brain and prevent much of the damage. This method may soon be entering
clinical trials to see if it can do the same for humans.
Though
the brain has its own means of recycling glutamate, injury causes the
system to malfunction, leading to glutamate build up. Prof. Teichberg
reasoned that this problem could be circumvented by passing glutamate
from the fluid surrounding brain cells into the bloodstream. But first,
he had to have a clear understanding of the mechanism for moving
glutamate from the brain to the blood. Glutamate concentrations are
several times higher in the blood than in the brain, and the body must
be able to pump the chemical "upstream." Glutamate pumps, called
transporters, are found on the outsides of blood vessels, on cells that
come into contact with the brain. These collect glutamate, creating
small zones of high concentration from which the glutamate can then be
released into the bloodstream.
Basic chemistry told him that he
could affect the transporter activity by tweaking glutamate levels in
the blood. When blood levels are low, the greater difference in
concentrations causes the brain to release more glutamate into the
bloodstream. He uses an enzyme called GOT that is normally present in
blood to bind glutamate chemically and inactivate it, effectively
lowering levels in the blood and kicking transporter activity into high
gear. In their experiments, Teichberg and his colleagues used this
method to scavenge blood glutamate in rats with simulated traumatic
brain injury. They found that glutamate cleared out of the animals'
brains effectively, and damage was prevented.
Yeda, the
technology transfer arm of the Weizmann Institute, now holds a patent
for this method, and a new company based on this patent, called
"Braintact Ltd.," has been set up in Kiryat Shmona in northern Israel
and is currently operating within the framework of Meytav Technological
Incubator. The US FDA has assured the company of a fast track to
approval. If all goes well, Phase I clinical trials are planned for the
near future.
The method could potentially be used to treat such
acute brain insults as head traumas and stroke, and prevent brain and
nerve damage from bacterial meningitis or nerve gas. It may also have
an impact on chronic diseases such as glaucoma, amyotrophic lateral
sclerosis (ALS) or HIV dementia. Teichberg: "Our method may work where
others have failed, because rather than temporarily blocking the
glutamate's toxic action with drugs inside the brain, it clears the
chemical away from the brain into the blood, where it can't do harm
anymore."
Prof. Vivian I. Teichberg's research is supported by
the M.D. Moross Institute for Cancer Research; the Nella and Leon
Benoziyo Center for Neurosciences; the Carl and Micaela Einhorn-Dominic
Brain Research Institute; the Mario Negri Institute for Pharmacological
Research -- Weizmann Institute of Science Exchange Program; the Ruth
and Samuel Rosenwasser Charitable Fund; the estate of Dr. Frank
Goldstein, Chevy Chase, MD; Mr. and Mrs. Irwin Green, Boca Raton, FL;
and the estate of Anne Kinston, UK.
Note: This story has been adapted from a news release issued by Weizmann Institute of Science.
http://www.sciencedaily.com/releases/2007/01/070117134104.htm
See also:
|
