Grant: Project Grant

The chronic exposure of people with Parkinson's disease (PD) to levodopa, the gold standard medication, mostly leads to the development of abnormal involuntary movements called dyskinesias that reduce the quality of life and are difficult to treat. Dyskinesias involve too much activity of the brain. The anti-dyskinesia medication (amantadine) brings also debilitating side effects. Our idea is to calm-down the brain with magnetic stimulation to decrease dyskinesia. This is a safe approach, noninvasive, painless and with no side effects. However, it is not understood yet how magnetic stimulation should be combined with levodopa (anti-parkinsonian medication) to efficiently decrease dyskinesias. The present project will test, in parkinsonian monkeys with dyskinesias, if brain magnetic stimulation or its combination with a drug treatment could help decrease dyskinesias more than drugs alone. The combination "magnetic stimulation + drug" may reduce dyskinesias at lower doses of drug (than drug alone) thus with smaller side effects of the drug. This will be tested with two drugs (amantadine then AV-101, a novel drug reported to reduce dyskinesias without side effects in animals and found to be safe in humans). The project proposes: to test if already present dyskinesias (due to chronic levodopa intake) can be decreased more extensively and rapidly by the combination "magnetic stimulation + drug" than by the drug alone. The project will test female and male monkeys considering that Parkinson's disease is more prevalent in males while more women have dyskinesias. The knowledge acquired will have a significant impact in clinical practice to better reduce dyskinesias a priority for PD.