The overall goal for the three years of our grant support has been to develop viable candidate drugs to reduce the known pathologies of Alzheimer Disease (AD). Previous years, we have been able to validate a robust hIPSC-screening assay based on these pathologies to uncover some interesting and reproducible potential drugs, including some drugs currently FDA approved and in common use for other human diseases.
In the past year of this grant, we have successfully screened optimized versions of these potential drugs to determine any increases in treatment potency and have identified several promising new drugs. In the course of our studies, we have discovered a novel kinase-driven mechanism, leading to increases in AD tangles. Many of our newly characterized drug candidates regulate similar pathways in other systems by blocking specific kinase actions. Thus we have opened the door to future large-scale screens of both known and unknown signaling blockers, for which large chemical small molecule libraries exist.
Between optimizing our screening assay and waiting for compounds, we still have significant work to complete to meet our prime objective. In the near future, we plan to continue careful analyses of our identified drugs for both mechanism of action and treatment efficacy in AD variant cell types, prior to initiating controlled preclinical mouse model studies. Our overall goal of identifying promising small molecule treatments for this devastating disease remains undiminished.