Professor Frank Gunn-Moore
University of St Andrews
Novel drugs for treating Alzheimer's disease
Previously, we have identified a drug target, amyloid binding alcohol dehydrogenase (also called 17b hydroxysteroid dehydrogenase type 10, ABAD), which we and others have shown, that if inhibited can prevent both mitochondrial and synaptic dysfunction and thus prevent the subsequent memory loss in living Alzheimers disease animal models. From a previous Alzheimers Society awarded grant, and more recently from a collaboration with an industrial pharmaceutical partner, we have identified three series of small molecular inhibitors. Some of these compounds we have synthesized are novel, while others are drugs for the treatment of other diseases, but have not yet been tested in Alzheimers disease models, though all have nanomolar IC50 values. Therefore, in this two year proposal, we wish to advance these compounds through to the next level of cellular testing and medicinal chemistry to obtain lead compounds. Specifically, we have developed a series of cell based assays in order to test them for their inhibition of ABAD, protection against amyloid induced cell damage, but also their general drug like properties including toxicity and blood brain barrier permeability. Compounds will be entered into our pipeline and if required, chemically modified to improve the desired bioavailability properties, allowing them to progress into being tested in living animal models for the disease.