A new approach in the hunt for Alzheimer’s drugs stops malformed proteins

The new technique could be the key to finding a successful drug for Alzheimer’s.
The new technique could be the key to finding a successful drug for Alzheimer’s.
Image: Reuters/Christian Charisius
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Alzheimer’s disease has stumped scientists and drug companies for a full century since its discovery. Experts largely suspect that the illness is a degradation of the brain caused by buildups of malformed proteins called amyloid beta, but, so far, no one has found anything that can stop these proteins from developing in those stricken with the disease.

The result: there’s has been no drug approved to treat the disease in over a decade. Yesterday (Sept. 24), however, researchers from the University of Cambridge and Lund University published evidence that a technique called “chemical kinetics” could hold the answer. Chemical kinetics is a methodology that looks how compounds move in the presence of other compounds; in this case, the scientists successfully used it to identify compounds that could interrupt harmful amyloid beta’s folding process. The team believes the approach could pinpoint many potential drugs in the future. This method of drug detection would be the first to tackle these misshapen proteins as they form, which would put a stop to the disease.

Amyloid beta is a protein that naturally occurs in all of our brains as part of its everyday function. Normally, the brain is able to dispose of it to prevent buildups from occurring. Even if amyloid beta forms incorrectly, sprightly young brains are able to get rid of it effectively before it accumulates.

The trouble occurs in older adults stricken with Alzheimer’s, whose brains become less effective at getting rid of waste. “It’s like a household recycling system: if you have an efficient system in place then the clutter gets disposed of in a timely manner. If not, over time, you slowly but steadily accumulate junk that you don’t need,” Michele Vendruscolo, a chemist at Cambridge and one of lead researchers on the team, said in a statement. These deformed amyloid proteins build up in thick plaques that gradually destroy various areas of the brain. By the time symptoms of the disease show up, damage to the brain is irreversible.

The team published initial work showing the potential of its chemical-hunting technique in the Proceedings of the National Academy of Sciences. As a proof-of-concept, they identified one form of an organic compound that inhibits atypical amyloid beta in test tubes and roundworms. This compound still needs to go through development and testing before it makes it to market. The team anticipates they will have a clinical trial in the works in as little as two years.

Misfolded proteins are thought to play a role in several other diseases, including Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis, or ALS. Ideally, the chemical kinetics used here could be used find the drugs that stop these conditions before they start.