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Bitopertin to Alleviate Dyskinesia in Parkinson's Disease

Study Rationale:
Levodopa-induced dyskinesia is abnormal involuntary movements that can affect people with Parkinson's disease after years of treatment. Available therapies for dyskinesia are only partly effective to alleviate the abnormal movements, and dyskinesia remains a hindrance to quality of life. Several experimental treatments for dyskinesia have focussed on a chemical substance of the brain called "glutamate." Glycine transporter 1 (GlyT1) inhibition is a way to safely enhance glutamatergic transmission that is well tolerated in clinical settings. Bitopertin is a potent, highly selective and clinically ready GlyT1 inhibitor.

We propose inhibiting GlyT1 with bitopertin will lead to indirect enhancement of the actions of glutamate and diminish the severity of dyskinesia.

Study Design:
We will test the effect of the drug in an experimental model of Parkinson's disease. We will assess the effect of this drug on dyskinesia and will also seek to determine if its effect is maintained over a prolonged administration. We will also investigate if the drug can prevent dyskinesia from appearing.

Impact on Diagnosis/Treatment of Parkinson's Disease:
Dyskinesia remains an important problem that undermines the quality of life of many people with Parkinson's disease. Our project bears the potential to offer a new, hopefully more effective, treatment to reduce dyskinesia and improve quality of life.

Next Steps for Development:
Our work is the first step in the characterization of our novel therapeutic paradigm. Following positive outcomes, we aim to further characterize the effect of our new treatment strategy in other models of parkinsonism, following which we hope to be able to offer it to humans in the context of clinical studies.


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