Novel Alzheimer’s Disease Treatment Methodology

Dementia is a neurocognitive disorder characterized by problems with memory, thinking and behavior.  Alzheimer’s Disease (AD) is the most common form of dementia, and is caused by accumulation of a variety of Abeta peptides as oligomers (chains of amino acids) and amyloid plaques in the brain. These neurotoxic Abeta peptides are created when enzymes cleave a large protein called amyloid precursor protein (APP) into smaller Abeta peptides of varying toxicity.

Now, scientists from the University of California, San Diego School of Medicine, the Medical University of South Carolina and San Diego-based American Life Science Pharmaceuticals, Inc. have implicated a new gene in AD that could be silenced or reduced in function to prevent progression of AD symptoms.  This gene, CTSB (which produces the protein cathepsin B), is responsible for the production of pGlu-Abeta peptides, known to be the most toxic form of the Abeta peptides.

In the past, researchers focused mainly on the BACE1 protein (from the BACE1 gene) because it is responsible for the actual cleavage of APP into toxic Abeta peptides.  While the research team silenced both BACE1 and CTSB, they found that only CTSB silencing completely removed pGlu-Abeta peptides from their mouse model.

Most excitingly, the team demonstrated that a small molecule called E64d could inhibit the functioning of cathepsin B, successfully preventing the formation of pGlu-Abeta peptides and relieving the mice of their cognitive difficulties.  As E64d is already FDA approved for treatment of muscular dystrophy, the researchers believe that once the dosages are calculated, the drug treatment could speed through clinical trials.  While there are current symptom and palliative care treatments available for individuals suffering from AD, no drug currently slows, stops, or reverses progression of AD symptoms.  No new drug for AD has been approved in over a decade.

This could not have come at a better time, as a spate of recent studies have shown the burden of AD is increasing.  A new report indicates that for the first time, women over 60 are almost twice as likely to get AD as they are to get breast cancer (1 out of 11 for breast cancer, 1 out of 6 for AD).  Another new study shows that although official reports dictate that 83,000 people died from AD in 2010, the deaths per year could total well over 500,000, moving AD from the sixth leading cause of death to the third, behind heart disease and cancer, respectively.  Finally, Alzheimer’s Association predicts that by 2050 the yearly costs in the US alone for caring for individuals with AD will top $1.2 trillion, up from less than $500 billion in 2013.

Although the underlying cause of AD is not completely known, there are ways to stave off symptoms.  These include regular exercise, quality sleep, and an active social life.  The Alzheimer’s Association’s website has many more tips, as well as information on the disease and ways to care for an individual suffering from AD.

Edward Marks is a PhD student at the University of Delaware.  His research involves the healing of burns and other chronic wounds using nanomedicine techniques, with the goal of pushing any advancement directly into the clinic.  Edward received his BS from Rutgers University and Masters from the University of Delaware.