Dyskinesias are unwanted movements associated with conditions such as levodopa treatment in Parkinson’s disease, antipsychotic medication in schizophrenia, and Huntington’s disease. Although the origins of these conditions can vary, they share a common underlying dysfunction in the neural circuitry of the basal ganglia. Currently approved drugs for dyskinesia are limited, and act primarily through modulating dopamine release. At higher doses, these drugs–such as amantadine–can elicit side effects that have prevented their widespread adoption.
At MapLight, we are taking a precisely targeted approach. Rather than interfering with dopamine release across the brain, our therapeutics will target a small subset of neurons in the basal ganglia that respond to dopamine, and which have been shown to change their firing during dyskinesias. These cells are also among the first to show changes during the progression of Huntington’s disease. By focusing our therapeutic strategies on specific populations of neurons that become dysfunctional during dyskinesia, our treatments will have both improved efficacy and fewer side effects.