Potential new drug candidate found for Alzheimer's disease

Researchers at the University of California, San Diego, the Medical University of South Carolina and American Life Science Pharmaceuticals of San Diego have demonstrated that oral administration of a cysteine protease inhibitor, E64d, not only reduces the build-up of ß-amyloid (Aß) in the brains of animal models for Alzheimer's disease, but also results in a substantial improvement in memory deficit. 

A paper detailing the findings has been published as an early online version and is scheduled for publication in the 6 September issue of the Journal of Alzheimer's Disease.

According to lead investigator Vivian Y H Hook, PhD, professor of the UCSD Skaggs School of Pharmacy and Pharmaceutical Sciences and professor of neurosciences, pharmacology and medicine at the UCSD School of Medicine, this is major news for scientists studying Alzheimer's disease. 

''The finding is especially exciting because E64d has previously been shown safe for use in humans, so we believe the compound has strong potential as a new therapy for Alzheimer's disease,'' said Hook.

Increased Aß levels in the brain are associated with the development of memory loss and amyloid plaque, the hallmark of Alzheimer's disease.  Aß peptides are ''cut'' out from a larger protein called the amyloid precursor protein (APP) by an enzymatic ''scissor'' called ß-secretase, and aggregate to form plaques in the brain regions responsible for memory. 

E64d reduces Aß by inhibiting the ß-secretase ''scissors'' from ''cutting'' the APP chain into smaller toxic Aß peptides. But in this study, the researchers found that the compound actually increases the activity of a protease called BACE1 which, to date, has been regarded as the primary ß-secretase.  Instead, E64d appears to lower brain Aß by inhibiting the ß-secretase activity of another protease, Cathepsin B.