Promising results from a new mouse study suggest there may be a way to halt the formation of a faulty protein that clogs up the brain in people with Alzheimer's disease.

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The researchers believe if the findings translate to humans, the new compounds could stop Alzheimer's disease in its tracks.

Writing in the journal PLOS ONE, researchers from the University of California-San Diego (UCSD) School of Medicine and Cenna Biosciences, Inc. describe how they identified compounds that block the production of beta-amyloid peptides in mice.

The team suggests if the findings translate to humans, then the most promising of the new compounds - which they refer to as P8 - could be given to people at high risk of developing Alzheimer's disease long before the signs of dementia appear.

Lead author Nazneen Dewji, an associate adjunct professor in the Department of Medicine at UCSD, says:

"We are blocking the actual production of beta-amyloid in a new way. It's very promising because it means that, in principle, we can stop the disease in its tracks."

She and her colleagues believe it is likely the new drug would have few side effects because of how it acts specifically on one target - amyloid precursor protein (APP).

New compounds specifically target APP

Exactly what causes the brain to waste away in Alzheimer's disease is not clear, but scientists believe the abnormal amounts of faulty proteins in the form of amyloid plaques and tau tangles found in the brains of people who have died with the disease have something to do with it.

The malformed proteins interfere with the effective working of brain cells, resulting in the host of cognitive and movement impairments that are associated with Alzheimer's disease, which accounts for up to 80% of all cases of dementia in the US.

The researchers explain that other experimental drugs that tackle amyloid proteins target the enzymes that cleave beta-amyloid from its larger precursor protein APP.

But those experimental compounds have largely failed in trials, Prof. Dewji says, "mostly because they are responsible for cleaving other proteins besides APP. Inhibiting or modifying their activities creates many undesirable effects in the cell."

The P8 compound in this new study does not act on enzymes - it binds to APP and blocks the process that cuts it up into the smaller amyloid peptides.

P8 and the other related compounds that the team has developed are made from a fragment of a membrane protein called presenilin 1 that is known to interact with APP to produce beta-amyloid.

The team was able to show how well P8 bound only to APP using both biophysical methods and optical imaging techniques.

2-week treatment led to 50% reduction in amyloid plaques in mice

Prof. Dewji - who is also president and CEO of Cenna, the biopharmaceutical company in La Jolla, CA, where the compounds are being developed - explains:

"Our approach is different, specific and interferes with only the reaction that produces beta-amyloid, as opposed to drugs that target the enzymes responsible for its cleavage from APP, which can affect multiple reactions in cells."

For their study, she and her colleagues carried out experiments in cell culture and mice engineered to produce large amounts of the human beta-amyloid early in life.

They found that on average, compared with untreated mice, the treated ones showed a 50% or more reduction in amyloid plaque accumulation following a 2-week course with either P8 or another of the candidate compounds, P4.

Prof. Dewji concludes:

"We now have a new approach for the treatment of Alzheimer's disease that can arrest the production of beta-amyloid very early and specifically. It's a real chance at a successful treatment for Alzheimer's disease."

Meanwhile, Medical News Today recently learned about another study where scientists found a potential cause of Alzheimer's disease in the immune system. There, a team from Duke University in Durham, NC, found that in the early stages of Alzheimer's, some immune cells that normally protect the brain begin instead to chew up arginine, an important amino acid.