Although the cause of levodopa-induced dyskinesia is still unclear, these motor complications appear to be due to abnormal dopamine transmission in the brain. Compelling evidence has highlighted a key role of neurosteroids (steroids that are capable of regulating neuronal activities) in the modulation of the dopaminergic system. We recently demonstrated that 5-alpha reductase activity, a key enzyme for the biosynthesis of neurosteroids, regulates dopaminergic signaling in brain areas involved in levodopa-induced dyskinesia. Interestingly, the 5-alpha reductase inhibitor finasteride has also been shown to exert therapeutic effects in patients with movement disorders related to imbalances of dopamine signaling, such as schizophrenia and Tourette syndrome.
We hypothesize that inhibition of 5-alpha reductase by finasteride is able to counteract dyskinesia in a pre-clinical model of Parkinson’s disease.
We will test the effects of chronic treatment with different doses of finasteride on dyskinesia in parkinsonian models with induced dyskinesia by daily treatment with levodopa. Then the dyskinetic models will be daily injected with different doses of finasteride for two to three weeks to establish the long-term effect on dyskinesia and the best dosing regimen.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
Finasteride is a licensed drug currently available for the management of benign prostatic hyperplasia and androgenic alopecia. If shown effective in controlling levodopa-induced dyskinesia, this therapy may be accelerated through clinical testing and beneficial to people with Parkinson’s experiencing these motor fluctuations.
Next Steps for Development:
Should our promising preliminary data be confirmed, this project may rapidly translate into a clinical investigation.