We need to find a drug or combination of drugs that can effective eliminate motor symptoms of Parkinson's disease without causing dyskinesia. Scientists are working several types of drugs that appear to be promising. Adenosine A2A antagonists (e.g., istradefylline) reduce overactivity in dopamine neurons that are thought to contribute to dyskinesia. In a recent study istradefylline reduced "off" time by 3/ of an hour per day compared with placebo, but did not reduce dyskinesias. AMPA antagonists (e.g. Talampanel, Perampanel ) reduce dyskineasia indirectly by blocking chemicals that excit dopamine neurons. Talampanel has been shown to reduce levodopa-induced dyskinesias in a monkey model of PD. Perampanel and Talampanel are currently being evaluated in clinical trials. The alpha-2 adrenergic receptor antagonist fipamezole has been reported to reduce levodopa-induced dyskinesias in animals and is currently in phase 2 studies. The dopamine agonist SLV308 (Pardoprunox) has been reported to reduce dyskineasia in animals and is currently in phase 3 trials.

New studies are offering hope for treatment of dyskinesias. One set of potential therapies that can effectively treat dyskinesias are based on the observation that delivering a steady amount of levodopa to the brain over the course of day (instead of ingesting large doses once or twice a day) can reduce dyskineasias. Continuous subcutaneous (under the skin via needle or pump) infusion of the dopamine drugs apomorphine and lisuride are currently undergoing the regulatory approval process in the United States. Lisuride is a dopamine agonist that is approved for the therapy of PD in Europe but not in the United States. Transdermal formulations of lisuride (lisuride TTS) have been developed to provide continuous delivery of the drug to the brain. Lisuride TTS is currently being tested in phase 2 trials in the United States and Europe. Continuous intraintestinal (through the intestine) infusion of levodopa has been shown to effectively reduce dyskinesias. This therapy however has still to make its way through the regulatory process before it becomes available to you.

What are th early signs of PD? many scientists have speculated that early PD may be characterized by a loss of sensitivity to certain rewards or pleasurable events because dopamine is important to processing 'reward' and pleasure. Scientists recently tested that idea in people with early PD before they were medicated with drugs that enhance dopamine and AFter they were treated with dopamine. They found that never-medicated patients with Parkinson's disease showed selective deficits on reward processing and that these deficits were eliminated after treatment with dopamine drugs. However for some persons with PD other abnormalities of reward processing emerged after treatment. Patients treated with the dopamine agonists showed signs of abnormal 'punishment processing'. they in effect paid too much heed to rewarding aspects of an event and no heed to punishing or harmful aspects of a situation. These findings can help us identify people at risk for PD (those insensitive to reward) and those persons with PD who are at risk for 'impulse control disorders' like gambling and sexual improprieties. These would be the patients on dopamine agonists who give too much weight to rewarding events and not enough weight to potentially harmful events.

Source: Reward-learning and the novelty-seeking personality: a between- and within-subjects study of the effects of dopamine agonists on young Parkinson's patients Brain Advance Access published on May 4, 2009.

The Parkinson’s Disease Foundation (PDF) is now accepting applications for 2009 Clinical Research Learning Institute (CRLI) to be held October 15th through October 17th. In this blog and this website I have urged people with Parkinson's disease to consider participating in research on PD, particularly clinical trials of new treatments. This multi-day training provides people with Parkinson’s disease with all they need to know to both participated wisely and to advocate for more and better research on PD. The program also teaches people with PD how to serve as representatives on Institutional Review Boards (IRBs) and Data Safety Monitoring Boards (DSMBs); that are integral to clinical trials. This year’s CRLI will be held at the Hamilton Park Hotel & Conference Center in Florham Park, NJ and is free of charge, with PDF also assuming the costs for participant travel and accommodations. An application can downloaded from the PDF website at http://pdf.org/en/crli. The deadline for applying is July 17, 2009.

SOURCE: http://www.pdf.org/