We hypothesize that our lead therapy, CT-526, has the capability to halt or even reverse neurodegeneration in patients with frontotemporal dementia (FTD).

Human and animal evidence shows that our target enzyme, CDK5, may become hyperactive and cause the underlying toxic processes in tauopathy, or diseases of tau such as FTD. Elegant genetic mouse and human stem cell studies demonstrate that the cleavage of the CDK5 activator, p35, produces a toxic protein, p25 which hyperactivates CDK5 and leads to cell death. Cogentis Therapeutics is developing a peptide, CT-526, which enters the brain, normalizes CDK5 hyperactivity, thereby reducing inflammation and cell death in multiple mouse models. Further testing is required before this therapy can be tested in human trials, and this proposal will facilitate that work.

In this proposal, we will measure CT-526 levels in the brain and find the ideal dose range to achieve the desired effect.  This data will give us the knowledge necessary to prepare for human trials in the Investigational New Drug application with the Food and Drug Administration.