Study Rationale: Excess CDK5 protein kinase activity in the brain caused by the binding of CDK5 with another protein called P25 has been connected to Parkinson's disease. The CDK5-P25 interaction can promote toxic processes, such as inflammation, cell death and protein aggregates (Lewy bodies). Cogentis Therapeutics is developing CT600, a peptide drug shown to enter the brain and disrupt the CDK5-P25 interaction, to treat Parkinson's disease. Preliminary small pre-clinical model data shows the success of the peptide approach.
Hypothesis: We hypothesize that CT600 will reduce this harmful CDK5-P25 interaction, stopping progression of Parkinson's disease-related changes in the brain, ultimately improving symptoms in patients.
Study Design: We will re-demonstrate in great detail that CT600 can enter the brain by treating small pre-clinical models with CT600 and measuring its levels in the brain and blood over time. Using a Parkinson's disease model, we will demonstrate that CT600 can reach its target (CDK5-P25 complex) in the brain by measuring changes in CDK5 activity and Parkinson's disease-related CDK5 protein targets (proteins that are changed by CDK5) and quantify its potential to reduce Parkinson's disease-related changes in the brain. Finally, we will validate our blood test designed to measure brain changes related to P25, helping to identify patients who will benefit from CT600 while also monitoring improvements after treatment.
Impact on Diagnosis/Treatment of Parkinson’s disease: CT600, which can disrupt a known mediator of Parkinson's disease-related changes in the brain, is poised to shift the treatment paradigm for this disease and improve quality of life. It’s unique mechanism of action is complementary to other approaches under development in the industry, offering both standalone and synergistic potential.
Next Steps for Development: Successful completion of this project will advance CT600 to critical IND-enabling studies needed prior to performing a Phase 1 clinical trial, an important step to bringing the drug to patients.