Levodopa, the standard treatment for Parkinson’s disease, offers effective symptom relief. However, it often fails to adequately address non-motor symptoms, and its long-term use may result in motor fluctuations and dyskinesia.

The paper reports a preclinical work performed by at the Department of Medical Translational Biology, Umeå University, Sweden and Integrative Neurophysiology, Lund University, Sweden, in collaboration with scientists at IRLAB. The recent study examines the effects of IRLAB’s drug candidate mesdopetam, amantadine and pimavanserin in a preclinical model of levo-dopa induced dyskinesia. It explores the mechanisms of levodopa-induced dyskinesia and the associated pharmacological strategies to alleviate dyskinetic symptoms.

The study elegantly shows that the reduction of a specific type of brain activity, narrow gamma band oscillations (NBGs), especially in the sensorimotor areas, correlates with decreased dyskinesias for both amantadine and mesdopetam. The findings suggest that diminishing NBGs is an essential biomarker for assessing the effects of antidyskinetic treatments. Additionally, the data offer insights into the systems-level mechanisms behind the antidyskinetic effectiveness of mesdopetam and suggest potential additional benefits for the treatment of Parkinson's-related psychosis.

“This is a comprehensive series of studies enabling in depth comparisons of the compounds. The results clearly illustrate the differences in effect profiles and action mechanisms, favoring mesdopetam as a treatment for dyskinesia,” says Nicholas Waters, EVP and Head of R&D at IRLAB.

The article Neurophysiological treatment effects of mesdopetam, pimavanserin, and amantadine in a rodent model of levodopa-induced dyskinesia is written by N Abdolaziz R et al.

The published article can be read in full here: https://onlinelibrary.wiley.com/doi/full/10.1111/ejn.70032