Combined Therapy with Amantadine and Fenobam for Levodopa-induced Dyskinesia
Dyskinesia Challenge, 2012
Amantadine is currently the only available medication to treat levodopa-induced dyskinesia: involuntary, jerky movements caused by long-term use of the Parkinsonís drug levodopa. However, the dose of amantadine that helps treat dyskinesia is associated with side effects such as cognitive impairment and with varied duration of efficacy. Therefore, an alternative or complementary treatment is sought. A compound called fenobam showed an effect on dyskinesia in pre-clinical models. This study will test the effects of amantadine and fenobam together in a Parkinsonís model. Since they work through different mechanisms, a combined effort may provide additional benefit than either alone.
Dyskinesia was induced in pre-clinical models, and then fenobam and amantadine were introduced orally ó both alone and together at doses ranging from 10-30 mg/kg. Research staff scored dyskinesia with a scale measuring duration of symptoms observed.
Relevance to Diagnosis/Treatment of Parkinsonís Disease:
Dyskinesia is a debilitating side effect of the current gold standard Parkinsonís treatment. A supplementary therapy that could alleviate the side effect without compromising the efficacy of levodopa would significantly improve the quality of life for people with Parkinsonís.
We expect the combined beneficial effect of amantadine and fenobam to be greater than the effect seen in both alone. If successful, we aim to determine a lowest maximal dose for alleviating dyskinesia with this combined therapy. Such a directive would inform next-stage clinical testing.
Amantadine and fenobam both reduced dyskinesia on their own at a 30 mg/kg dose, but lower doses did not see an effect. The combined amantadine and fenobaum significantly reduced dyskinesia without worsening Parkinsonís disability at a dose of 10mg/kg of fenobam and 20 mg/kg of amantadine. That is, when combining lower doses of the two drugs, which would be ineffective on their own, the additive effect was clinically significant, drastically reducing dyskinesia.
INSERM Research Director at Institute of Neurodegenerative Diseases, CNRS UMR 5293, University Victor Segalen
Location: Bordeaux, France