Funded Studies
Objective/Rationale:
In Parkinson’s disease, L-DOPA-induced dyskinesias (LID) are therapeutically limiting side effects that occur with long-term L-DOPA treatment, and their presence significantly diminishes the quality of life of these patients. Imbalances in endogenous opioid activity in brain regions that control movement are thought to contribute to the development and maintenance of LID, and compounds that act by selectively antagonizing mu opioid receptors (MOR), may be effective in the treatment of LID.
Project Description:
Adolor has demonstrated that a prototypic selective MOR antagonist is safe and effective in reducing LID in primate models, supporting the utility of MOR antagonists for the treatment of LID. The proposed studies will focus on chemical optimization, determination of antagonism at MOR and assessments of MOR receptor selectivity, and evaluation of the drug metabolism and pharmacokinetic properties of selected compounds. The overall objective of the project is to improve upon the chemical characteristics, biological activities and drug-like properties of MOR antagonists in order to identify compounds with suitable pharmaceutical properties that warrant further development and advancement into the clinic.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Currently, options for the treatment of LID are limited, and the appearance of LID in patients with Parkinson’s disease often limits the dose of L-DOPA that can be administered to the patient for control of Parkinsonian symptoms. The proposed studies will support the hypothesis that selective antagonism at MOR reduces the appearance of LID, and will provide drug candidates with potential therapeutic utility for the treatment of LID in patients with Parkinson’s disease.
Anticipated Outcome:
Adolor’s objective is to identify selective MOR antagonists with desirable pharmaceutical properties for advancement into primate efficacy and preclinical safety evaluations. Optimized drug candidates that meet advancement criteria will be assessed further in formal IND-enabling studies, and ultimately proof of concept studies in humans.