Objective: To assess the efficacy and safety of pridopidine in PD patients with Levodopa-induced dyskinesia (LID).

Background: Pridopidine is a small molecule in clinical development for HD and ALS with a well-established safety and pharmacokinetic profile. At high doses (>=100 mg bid), pridopidine targets and modulates the D3R, 5-HT1A and the adrenergic α2C receptors. As these targets are implicated in dyskinesia, pridopidine presents an attractive drug candidate for the treatment of levodopa-induced dyskinesia (LID), with a unique mechanism of action.

Method: Pridopidine was evaluated pre-clinically in the rat 6-OHDA model for levodopa-induced Abnormal Involuntary Movements (AIMs), and in the gold standard macaque MPTP model for LID. Plasma exposures at the effective doses in non-human primates (NHP) and rats were correlated to human doses producing similar steady state exposures.

Results: Pridopidine demonstrates a significant, dose dependent anti-AIMs effect in rats and anti-LID effect in macaques. In rats, pridopidine 15, 30 and 60 mg/kg reduces AIMs (up to 42%) and contraversive rotations (up to 93%). In the macaque, 20 and 30 mg/kg reduces LID (up to 71%) and the duration of on-time with disabling dyskinesia (up to 60%). Pridopidine does not compromise the beneficial anti-PD effects of levodopa.
Plasma exposure at the effective doses correlates with ~ 85% occupancy of the α2CR and D3R, and ~ 75% occupancy of the 5-HT1A receptor.

Conclusion: The ongoing gLIDe trial is an exploratory phase IIb trial designed to assess the safety and efficacy of pridopidine in reducing L-DOPA induced dyskinesia in PD patients as measured by the UDysRS (Unified Dyskinesia Rating Scale).
This abstract was previously accepted for presentation at AAT-AD/PD Focus meeting in April 2020.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/pridopidine-for-the-treatment-of-levodopa-induced-dyskinesia-in-patients-with-parkinsons-disease/