There remains an urgent and unmet need for novel Alzheimer’s disease therapeutics, with a limited number of drugs currently approved in Australia to treat symptoms of Alzheimer’s disease, and none that are able to slow its progression. One reason that drug candidates are ultimately ineffective against Alzheimer’s disease may be that insufficient drug reaches brain cells from the bloodstream, due to the tight barrier formed by blood vessels within the brain. Our research aims to engineer an Alzheimer’s disease drug that can bypass this barrier and enter the brain efficiently. We have developed HsTX1[R14A], a drug candidate that selectively targets microglia, the immune cells of the brain, by blocking a protein that is overactivated on these cells. This suppresses the inflammatory properties of microglia and promotes their ability to clear toxic proteins that build up in the brain in Alzheimer's disease. By attaching ‘shuttle’ molecules to HsTX1[R14A], which allow HsTX1[R14A] to enter the brain more easily, we aim to deliver a therapeutically effective drug dose to the brain (as tested in a mouse model). Together with its high efficacy and low toxicity, HsTX1[R14A] would be a highly promising lead molecule for development as a next-generation drug for Alzheimer’s disease.
At the time of award, Dorothy was an early career postdoctoral researcher based at the Monash Institute of Pharmaceutical Sciences.