Global Technology - January 2016

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According to the journal Aging, Salk Institute researchers have found that an experimental drug candidate intended to combat Alzheimer’s disease produces a host of anti-aging effects, as well.

The Salk team expanded upon their previous development of a drug candidate, called J147. In the new work, the team showed that the drug works well in a mouse model of aging not typically used in Alzheimer’s research.

When the mice were treated with J147, they demonstrated better memory and cognition, healthier blood vessels in the brain, and other improved physiological features.

The team initially designed a test to validate the drug in a novel animal model that was similar to 99 percent of Alzheimer’s cases. However, the researchers unexpectedly found that J147 made old mice look like they were young, based upon a number of physiological parameters.

Most Alzheimer’s drugs developed in the past 20 years target the amyloid plaque deposits in the brain, but none has proven effective in clinical trials. So, rather than target amyloid, the Salk team decided to zero in on the major risk factor for the disease — old age. Using cell-based screens against old age-associated brain toxicities, they synthesized J147.

The researchers used a comprehensive set of assays to measure the expression of all genes in the brain, as well as over 500 small molecules involved with metabolism in the brains and blood of three groups of the rapidly aging mice: one set that was young, one set that was old, and one set that was old but fed J147 as they aged.

The old mice that received J147 performed better on memory and other tests for cognition and also displayed more robust motor movements. The mice treated with J147 also had fewer pathological signs of Alzheimer’s in their brains.

Importantly, because of the large amount of data collected on the three groups of mice, it was possible to demonstrate that many aspects of gene expression and metabolism in the old mice fed J147 were very similar to those of the young animals.

These included markers for increased energy, metabolism, reduced brain inflammation, and reduced levels of oxidized fatty acids in the brain.

While these studies represent a new and exciting approach to Alzheimer’s drug...

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