Aging Well

Experimental Alzheimer's Drug May Also Fight Aging

An experimental drug aimed at fighting Alzheimer’s also has a number of anti-aging effects in animals, researchers say.

A team of experts from the Salk Institute, in La Jolla, California, expanded upon their previous development of a drug candidate, called J147, which takes a different tack by targeting Alzheimer’s major risk factor–old age. In the new work, the team showed that the drug candidate worked well in a mouse model of aging not typically used in Alzheimer’s research. When these mice were treated with J147, they had better memory and cognition, healthier blood vessels in the brain and other improved physiological features, as detailed November 12, 2015 in the journal Aging.

“Initially, the impetus was to test this drug in a novel animal model that was more similar to 99 percent of Alzheimer’s cases,” says Antonio Currais, the lead author and a member of Professor David Schubert’s Cellular Neurobiology Laboratory at Salk. “We did not predict we’d see this sort of anti-aging effect, but J147 made old mice look like they were young, based upon a number of physiological parameters.”

Alzheimer’s disease is a progressive brain disorder, recently ranked as the third leading cause of death in the United States and affecting more than five million Americans. It is also the most common cause of dementia in older adults, according to the National Institutes of Health. While most drugs developed in the past 20 years target the amyloid plaque deposits in the brain (which are a hallmark of the disease), few have proven effective in the clinic.

“While most drugs developed in the past 20 years target the amyloid plaque deposits in the brain (which are a hallmark of the disease), none have proven effective in the clinic,” says Schubert, senior author of the study.

Several years ago, Schubert and his colleagues began to approach the treatment of the disease from a new angle. Rather than target amyloid, the lab 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.

Previously, the team found that J147 could prevent and even reverse memory loss and Alzheimer’s pathology in mice that have a version of the inherited form of Alzheimer’s, the most commonly used mouse model. However, this form of the disease comprises only about 1 percent of Alzheimer’s cases. For everyone else, old age is the primary risk factor, says Schubert. The team wanted to explore the effects of the drug candidate on a breed of mice that age rapidly and experience a version of dementia that more closely resembles the age-related human disorder.


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