A potential new therapy for Alzheimer’s disease may be on the horizon after the discovery of a new compound.

Researchers at the University of California, San Diego, the Medical University of South Carolina and American Life Science Pharmaceuticals of San Diego have established that oral administration of a cysteine protease inhibitor – E64d, cuts down the build-up of β-amyloid (Aβ) in the brains of animal models for Alzheimer’s disease and also leads to a significant transformation in memory deficiency.

The study has been published in the online version of the Journal of Alzheimer’s Disease.

Lead researcher Vivian Y. H. Hook from the UCSD School of Medicine is excited about the finding mainly because E64d compound has strong potential as a new therapy for Alzheimer’s disease.

How E64d works

A rise in AB levels in the brain are related with the development of memory loss and amyloid plaque, the characteristic of Alzheimer’s disease.

AB peptides are “cut” from a larger protein called the amyloid precursor protein (APP) by an enzymatic “scissor” known as B-secretase, and aggregated to form plaques in the brain area responsible for memory.

E64d cuts down AB by inhibiting the B-secretase “scissors” from “cutting” the APP chain into little cyanogenic AB peptides.

However in this study, the researchers discovered that the compound in reality increases the activity of a protease called BACE1 that is primarily considered as B-secretase. Alternatively, E64d seems to lower brain AB by inhibiting the B-secretase activity of another protease, Cathepsin B.

Major finding

According to lead researcher 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 finding has boosted the confidence of scientists working on Alzheimer’s disease.

Hook stated that the study has shown Cathepsin B as a new target for remedial inhibition of Aβ production and consequent improved memory function.

The team studied both old and young transgenic Alzheimer’s disease mice, and discovered that memory loss was greatly enhanced. In young mice, feeding E64d stopped development of memory loss and in old mice with memory loss, it enhanced memory.

The study is based upon work published in March 2008 that first showed that inhibitors of Cathepsin B ended in increased memory and reduction of Aβ and amyloid plaque.

In the new study, oral administration of the drug was effective and could pave the way to clinical trials in humans.

Co-authors of the study were Gregory Hook, PhD, of American Life Science Pharmaceuticals in San Diego, and Mark Kindy of the Medical University of South Carolina, including as the Ralph H. Johnson VA Medical Center, and Applied Neurotechnology, Inc., in Charleston, SC.

The study was funded in part by the National Institute on Aging (1) of the National Institutes of Health and the Alzheimer’s Drug Discovery Foundation (2).

Alzheimer’s – facts

  • According to the latest data released by the Alzheimer’s Association (3) an estimated 5.4 million Americans have Alzheimer’s disease. One American develops Alzheimer’s disease every 69 seconds.
  • In 2010, 14.9 million family and friends provided 17 billion hours of voluntary care to those with Alzheimer’s and other dementias.
  • The total cost of caring for Alzheimer’s patients in America is expected to exceed $183 billion in 2011.
  • Deaths from Alzheimer’s rose by 66 percent between 2000 and 2008, and Alzheimer’s is the only cause of death among the top 10 in America without a definite prevention or cure.

1) National Institute on Aging
2) Alzheimer’s Drug Discovery Foundation
3) Alzheimer’s Association



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