Development of S-PCT3010 to treat Parkinson's Disease

Abstract Polycore Therapeutics is developing S-PCT3010, a pharmaceutically tractable small molecule which significantly reduces motor symptoms associated with Parkinson’s disease (PD). Parkinson’s disease (PD) is the second most common age-related neurodegenerative disease affecting 1% of people aged 60 or older in industrialized countries. Genetic, epigenetic and environmental factors are linked to its incidence. PD pathology is associated with progressive loss of dopaminergic neurons in the mid brain and the presence of Lewy bodies. The gold standard for treating motor impairment in PD is with levodopa (L-DOPA) or other dopamine receptor agonists. These therapeutics are highly efficacious in treating motor symptoms, however, chronic use of these medications lead to painful dyskinesias or impulse control disorders in addition to worsening of non-motor symptoms. S-PCT3010 is a novel dopamine receptor agonist but with significantly differentiated mechanism of action. S-PCT3010 was rationally designed to overcome the limitations of existing therapies and is predicted to reduce motor symptoms in PD patients without the risk of developing tolerance, on/off effects, dyskinesias or impulsive behaviors.In preliminary results, Polycore has demonstrated that S-PCT3010 is very efficacious in improving motor impairment in rodent models of PD. S-PCT3010 has very desirable drug-like properties. Based on the mechanism of action, S-PCT3010 and its parent molecule PCT-3010 only recruit the G-protein coupled pathway for signaling thus promoting improvements in movement, attenuates dyskinesias induced by L-DOPA and is not expected to induce impulsive behaviors. The specific aims for this Phase II SBIR grant will complete proof of concept studies in a regulatory compliant fashion for future IND submission.Narrative: Parkinson’s disease (PD) is the second most common age-related disease involving degenerating nerve function. Although treatments can be effective for moderating disease related loss of motor function, their effects wear off over time, and eventually cause tremors and abnormal movements. PolyCore Therapeutics is developing a new drug with the potential to improve treatment of PD over standard therapy, while avoiding drug tolerance and reducing dyskinetic side-effects.