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Parkinson's : Curing Dyskinesia

For patients suffering from Parkinson’s disease, the most common treatment, L-Dopa, is a difficult compromise. If it does reduce the slowness, stiffness, and tremors produced by Parkinson’s in the first place, it also leaves most patients with so little control of their muscles that they have difficulty standing or even sitting after a while. New research by Erwan Bézard’s team,1 at the University of Bordeaux, sheds light on L-Dopa’s dramatic side effects, and may help scientists find ways to counteract them.2
Nearly 6.3 million people suffer from Parkinson’s disease, a neuro-degenerative disorder in which the dopamine-producing neurons slowly disappear. L-Dopa compensates for the lack of dopamine in the brain, but as treatment continues, its side effects–known as dyskinesia– become progressively worse. After three years of treatment, dyskinesia affects 80% of all patients.
Bézard’s team had already shown that dyskinesia was connected to a decline in electrical activity in certain parts of the brain. Working with scientists in Sweden and England, they set out to discover the mechanism involved when L-Dopa begins producing unwanted effects. The results, obtained on primates, were so dramatic that the scientists thought they had made a mistake. “When you get a result like this, you have to be suspicious. It was almost too bad to be true. So we went back, rechecked everything, and got the same results,” explains laboratory director Erwan Bézard.
Tests showed that although the brain responded normally to the first dose of L-Dopa, the pattern of proteins expressed in a specific region of the brain (the striatum) changed irreversibly within one hour of the first exposure to the drug. The initial change was comparable to those observed after four or five months of treatment.
This discovery presents both good and bad news for people suffering from Parkinson. The research shows for the first time that damage to the patient’s brain begins immediately, with the first dose of L-Dopa. Since all Parkinson patients receive at least one dose, developing dyskinesia is “almost unavoidable,” according to Bézard.
Yet this discovery may help scientists develop a way to counteract L-Dopa’s negative side effects. By comparing the brains of animals that developed dyskinesia with those that did not, the research team identified more than 150 different proteins as well as several protein pathways that were affected by L-Dopa. This should help scientists identify target proteins for treatments that could prevent dyskinesia.

Anita Elash

Notes :

1. Laboratoire Mouvement, adaptation et cognition (CNRS / Université Bordeaux-I and II).
2. B. Scholz et al., “Striatal Proteomic Analysis Suggests that First L-Dopa Dose Equates to Chronic Exposure,” PLoS ONE, 2008. 3(2): e1589.

Contacts :

Erwan Bézard,
Institut des neurosciences de Bordeaux.


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