Over the past few decades, several intervention strategies have been tested without success against amyloid proteins known to damage and kill neurons in the brain eventually leading to Alzheimer’s. But scientists at NYU Langone Medical Center have identified a compound called 2-PMAP, which reduced the amyloid proteins by more than half in mice models, generating great excitement among doctors about a possible cure for this debilitating disease, according to a press release Tuesday.

The researchers hope that the drug made with this compound can be taken over several years without any potential side-effects. The research is to be published online on June 3 in the journal Annals of Neurology. "What we want in an Alzheimer's preventive is a drug that modestly lowers amyloid beta and is also safe for long term use. Statin drugs that lower cholesterol appear to have those properties and have made a big impact in preventing coronary artery disease. That's essentially what many of us envision for the future of Alzheimer's medicine," said lead researcher, Dr. Martin J. Sadowski.

Amyloid beta are the main components of the amyloid plaques that form deposits in the brain. They are formed when their precursor protein called amyloid precursor protein (APP) is cut by certain enzymes. Prolonged accumulation of these plaques results in Alzheimer’s and drugs for its prevention are targeted at reducing this accumulation. The quest for such anti-amyloid drugs came from the discovery of a mutation that slows down the production of amyloid beta by almost half. Not only does the mutation protect the brain from Alzheimer’s, but it also aids in maintaining cognitive ability and longevity.

But even with this knowledge the search for such a drug has not succeeded as the key to stopping Alzheimer’s is preventing its onset altogether. After screening a number of compounds, Dr. Sadowski and colleagues found the 2-PMAP compound, which successfully lowered the levels of amyloid beta's precursor APP when used even at low, non-toxic concentrations. 2-PMAP reduced the APP production in test cells and this subsequently reduced the amyloid beta levels by more than 50 percent. The compound was then tested on mouse models who had been genetically engineered to have conditions similar to those found in Alzheimer’s patients such as overproduction of AAP and amyloid plaque deposits. A five-day treatment with 2- PMAP not only lowered levels of AAP but also those of amyloid beta.

Four months of intensive treatment sharply reduced the amyloid deposits and prevented the cognitive deficits that are normally seen in these transgenic mice as they get older. Another advantage of 2- PMAP is that it is more efficient than other amyloid-lowering compounds, since it can cross efficiently from the bloodstream to the brain, and doesn't require too many additional chemical modifications that may make it less potent against APP.

The compound also appears to have a highly selective effect on APP production, by interfering with the translation of APP's gene transcript into the APP protein itself. Drugs that failed to successfully prevent Alzheimer’s, while cleaving amyloid beta from APP also interfered with other important functions of the enzymes. This research has greatly bolstered hopes of a drug that would prevent Alzheimer’s that is expected to afflict 16 million Americans over the age of 65 by 2050, according to the Alzheimer's Association.

Published by Medicaldaily.com