Prevent plaque formation

New drug prevents one of the causes of Alzheimer's disease

Georgy Golovanov, Hi-tech+

Amyloid plaques are pathological accumulations of peptides in the brain that trigger neurodegenerative changes and lead to the development of cognitive impairment. A group of American scientists has developed a new drug that prevents the development of Alzheimer's disease by modulating a key enzyme involved in the formation of amyloid plaques.

Article by Rynearson et al. Preclinical validation of a potential gamma-secretase modulator for Alzheimer's disease prevention is published in the Journal of Experimental Medicine – VM.

"Alzheimer's disease is an extremely complex and multifaceted condition that has not yet been effectively treated, let alone prevented," said senior researcher Stephen Wagner, a professor at the University of California, San Diego. "Our discovery indicates that there is a potential therapy that can inhibit one of the key elements of Alzheimer's disease."

Amyloid plaques consist of fragments of beta-amyloid proteins. These peptides are produced by the enzymes beta-secretase and gamma-secretase, which sequentially cut a protein called the amyloid precursor protein on the surface of neurons. Some of the resulting pieces, such as Aß42, are particularly susceptible to clusters, which lead to the onset of dementia.

In the past, scientists have tried to inhibit beta-secretase or gamma-secretase, but many of the drugs turned out to be toxic or unsafe for humans. Wagner and his colleagues undertook to study the therapeutic potential of gamma secretase modulators (MGS), which slightly change its activity, so that they produce less beta-amyloids, but continue to perform their functions.

Researchers have developed a new MGS and tested it on mice, rats and macaques. The results showed that low doses of the drug stop the production of Aß42 in rodents without provoking side effects. The drug also proved to be safe and effective for monkeys, reducing their level of amyloid plaques by 70%.

The authors of the study believe that the new drug can be used prophylactically, either in patients with genetic mutations that increase predisposition to Alzheimer's disease, or in cases where amyloid plaques are seen on brain scans.

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