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Parkinson's Drugs Undergoing Tests
Science Daily - After Parkinson's disease patients use the drug levodopa or
L-dopa for several years as a treatment for restoring the cellular
communication that controls muscle movement by replacing lost dopamine, they
begin to experience motor complications that include a shortened response to
each dose of L-dopa.

"As time goes on and the disease progresses, the off periods, that is, time
during which the medicine is not working at its best, come more frequently
as on periods, or times during which patients experience their best response
to the drug, last for shorter periods of time," explained Jay S. Schneider,
PhD, who heads the Parkinson's Disease Research Unit at Thomas Jefferson
University Hospital.
Parkinson's disease gradually destroys brain cells that produce dopamine. As
dopamine levels drop, symptoms increase: tremors in the arms, legs and face;
periodically stiff or frozen limbs; slow movement, particularly a shuffling
gait; and impaired balance and coordination.
Dr. Schneider, Professor of Pathology, Anatomy and Cell Biology and
Neurology at Jefferson Medical College of Thomas Jefferson University, and
movement disorder specialists Tsao-Wei Liang, M.D., Assistant Professor of
Neurology, Jefferson, and Daniel Erik Kremens, M.D., J.D., Assistant
Professor of Neurology, Jefferson, are spearheading a new clinical trial to
test a new anti-Parkinson's drug in an attempt to decrease such off-time
experiences and extend L-dopa's effectiveness.
The study will evaluate whether a drug, E2007, can significantly lengthen
the time that a patient's L-dopa medication is effective, reducing both the
amount of off time during the day, as well as other unwanted side effects of
L-dopa treatment. E2007 is non-dopaminergic drug that acts on a subclass of
receptors called the AMPA receptors, which mediate fast synaptic
transmission in the central nervous system.
Standard treatments for Parkinson's disease focus on restoring the cellular
communication that controls muscle movement by replacing lost dopamine with
L-dopa. While this therapy works well for a while, it can't stop the
disease's inevitable march - and the patient's decline. While one current
strategy is to focus on neuroprotective agents to modify disease
progression, another is to use so-called "adjuncts" that can have modest
effects on patients' off-times, when L-dopa can be ineffective for brief
periods.
"The hope is that by altering dopamine transmission through the modulating
the activity of AMPA receptors, there will be measurable effects on the
dopamine system," said Dr. Liang.
The study is designed for patients with more advanced Parkinson's who have
been taking L-dopa for some time and are now experiencing fluctuations in
its effectiveness.
Individuals must have at least two hours of off time a day. Groups of
patients will receive either one of two dosages of the drug or a placebo.
The trial is also aimed at evaluating E2007's safety, as well as how
patients tolerate it. The study will involve approximately 700 patients at
about 150 centers across the U.S., Canada, Australia, New Zealand and South
America. Jefferson hopes to recruit at least 12 patients.
"It's an interesting approach and an exciting trial because it is exploring
a drug in a new therapeutic category," said Dr. Kremens."L-dopa is still the
gold standard and we haven't come up with a better dopamine agonist as yet."
Note: This story has been adapted from a news release issued by Thomas
Jefferson University.

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