NEWS-Jefferson neuroscientists show drug may protect

[Judith Richards <judithr@xxxxxxxx>]

EMBARGOED FOR RELEASE: 29 JUNE 2001 AT 08:00 ET US

     Contact: Steve Benowitz
     steven.benowitz@xxxxxxxxxxxx
     215-955-5291
     Thomas Jefferson University

Jefferson neuroscientists show drug may protect against brain cell
damage in Parkinson's

Researchers at Jefferson Medical College have shown in the laboratory
that a new drug already given to some patients who are in the early
stages of Parkinson's disease may actually protect brain cells from
dying and perhaps eventually be used as a prophylactic agent for the
disease.

"If you could get to patients as early as possible after diagnosis and
provide a neuroprotective therapy, you might be able to stop or
dramatically slow further loss of nerve cells, effectively maintaining
the disease in its early stages," says Jay Schneider, Ph.D., professor
of pathology, anatomy and cell biology and neurology and Director of the
Parkinson's Disease Research Unit at Jefferson Medical College of Thomas
Jefferson University in Philadelphia, who led the work. Dr. Schneider
and his co-workers report their results June 29 in the journal Brain
Research.

The drug, pramipexole (PPX), belongs to a class of drugs called dopamine
agonists, which act directly on dopamine receptors, simulating the
activity of dopamine. Parkinson's disease results from a lack of
dopamine-producing cells. PPX is frequently given to early-stage
patients in the hope of improving symptoms and delaying the need for
another anti-Parkinson's drug, levodopa. The researchers studied both
young and old mice that had been given a neurotoxin that in turn caused
a Parkinson's-like condition.

To assess the neuroprotective properties of PPX, some mice were given
the drug at the same time they were given the toxin. Some of these
animals continued to receive PPX for several days while others received
the drug for as much as two weeks. Others did not receive the drug.

The effect of the drug was "dramatic," Dr. Schneider says, and more
pronounced in the younger animals. "We were able to prevent nearly 100
percent of the brain cells from dying, which is amazing. It seems like
the greatest effect came when giving both the toxin and drug at the same
time and then continuing the drug for another two weeks," he says.

Dr. Schneider and his co-workers think that PPX may somehow interfere
with apoptosis, or programmed cell death, and perhaps other early
death-related mechanisms set into motion early in the cell death
process.

Dr. Schneider's team also found that the size of the dopamine cells was
significantly greater in the animals who received the toxin and
treatment simultaneously and continued to have the treatment for 14
days, suggesting that "in addition to its possible anti-apoptotic
effects, the drug may work directly or indirectly as a neurotrophic
factor - it may actually enhance the cells," he says.

Dr. Schneider says that although the way in which PPX exerts its
neuroprotective effect is not known, he and his  colleagues believe that
the neuroprotective effects of the drug are not related to its ability
to act on dopamine receptors. Researchers don't know the drug's
long-term effects or how much it might help slow the progression
of the disease, he notes.

Some patients show symptomatic benefit from the medication. But it has
side effects, such as excessive daytime sleepiness, and rarely, sudden
onset of sleepiness. "One of the problems in showing a neuroprotective
effect in patients is knowing how much of a dose to give," he says. "The
neuroprotective dose in a mouse may be higher than the highest tolerable
dose in a human.

The scientists currently are doing studies to try to understand the
mechanisms behind the drug's neuroprotective effects. A key will be to
first understand the way in which cells die after exposure to the
neurotoxin, Dr.Schneider says.

 In related work, Dr. Schneider's group is looking for patients to help
them find out whether a promising, drug, GM1 ganglioside, can improve
symptoms, delay disease progression, and in some cases actually restore
damaged brain cells in Parkinson's disease patients.
Dr. Schneider is leading a five-year study involving 150 patients. The
researchers want to compare the effectiveness of GM1 ganglioside - a
naturally occurring substance that plays an important role in cell
growth, development, and repair - to standard Parkinson's disease
treatments, which improve symptoms but do not affect the disease
process.

For more information, call 1-800-JEFF-NOW.

                                              ###

Contact:Steve Benowitz or Phyllis Fisher at 215-955-6300. After Hours:
215-955-6060.


--
Judith Richards, London, Ontario, Canada
judithr@xxxxxxxx
                        Today?s Research...
                                Tomorrow?s Cure

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