The latest success in Alzheimer’s drug development is Lecanemab, an antibody drug that patients need to visit hospitals regularly for infusion.  The goal of this project is to develop a small molecule treatment, which is much cheaper and easier to dose, to slow cognitive decline in patients.  Our drug is designed to target and remove a specific pathological protein named tau, which misfolds and accumulates in the brains of people with Alzheimer’s disease.  The drug will harness the body’s own garbage removal system in a process called protein degradation to remove the disease-causing tau proteins.  The drug has two distinct structural domains, one binds specifically to the misfolded tau and another to a protein called E3 ligase.   Once the drug forms a complex with tau aggregates and E3 ligase it triggers the natural disposal system to clear the unwanted tau protein in the neurons, thus halting or slowing down the disease progression.  Drugs harnessing the E3 ligase degradation system are called PROTACs, an emerging technology showing promising clinical results for cancer treatment.

APRINOIA has been very successful in developing PET imaging tools for the visualization of protein aggregates such as pathological tau in patients.  We combine our unique experience and chemical collection of tau binding molecules with those binding to E3 ligase to create novel PROTAC drugs that can selectively degrade the pathological tau.  We have made significant progress to demonstrate that such molecules can indeed clear misfolded tau in cells and in animals when given by iv injection.  With the support from ADDF we will take on the next challenge to optimize the structure for a final drug product that can be taken as a pill.