In a recent newsletter we discussed the experimental drug E2007. It is currently in Phase III clinical trials, which means that it has a reasonably good chance that is will make it into the pharmacies in the next 2 - 5 years roughly. It would probably not be a wonder drug for Parkinson's disease, but it would add another dopamine agonist option for people.
After Parkinson's disease patients use the drug levodopa or L-dopa for several years to replace 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. c Dr. Schneider and movement disorder specialists Tsao-Wei Liang, M.D., 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. "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."