A research collaboration between two Cure Alzheimer’s Fund Research Leadership Group members, Berislav Zlokovic, M.D. Ph.D., and Robert Vassar, Ph.D. and Divna Lazic, Ph.D., resulted in new data suggesting that a drug currently in clinical trilas to be used to help the brain recover from stroke also has the potential to play a preventative role in early-stage Alzheimer’s disease.

The research was published in the Journal of Experimental Medicine and profiled on the website for the journal Nature.

First author, Divna Lazic, and colleagues found that a drug that has been developed for use in stroke has the potential to prevent Alzheimer’s disease. The drug compound referred to as 3K3-APC protected the brains of a mouse-model of Alzheimer’s disease by both reducing the build-up of toxic amyloid plaques and ameliorating memory impariments.

3K3-APC itself is a genetically modified version of protein C, a human blood protein, which reduces inflammation and protects neurons and the cells that line the walls of blood vessels from degeneration. 3K3-APC has already been found to play a therapeutic role in mouse models of traumatic brain injury and multiple sclerosis. This drug has already been shown to be safe in human clinical trials aimed at treating stroke and reducing intracerebral bleeding.

In an interview, Dr. Zlokovic reported that because the drug has been found to be neuroprotective and vasculoprotective in multiple models of neurological disorders, he wanted to investigate whether 3K3-APC could also protect the brain from the toxicity of amyloid plaques in a mouse model of Alzheimer’s disease. This drug significantly reduced the accumulation of amyloid plaques in the brains of mice and had the added benefit of maintaining normal cerebral blood flow. The mechanism of action of this drug is the inhibition of BACE1 – an enzyme that is required to produce amyloid plaques. BACE1 inhibitors have been tested in clinical trials for Alzheimer’s disease with no demonstrated therapeutic success for Alzheimer’s patients. 3K3-APC blocks the production of BACE1 at earlier stages of the disease providing a new angle for preventing amyloid plaque accumulation.

http://jem.rupress.org/content/216/2/279