Researchers at Salk Institute were researching a potential drug treatment for Alzheimer’s and made a very exciting and unexpected discovery. The drug had a host of unexpected anti-aging effects in animals.
When the Salk team treated mice with J147, they had better memory and cognition, healthier blood vessels in the brain and other improved physiological features, as detailed in the study published on November 12th 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,” said 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. Alzheimer’s is also the most common cause of dementia in older adults.
“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,” said Schubert, senior author of the study.
Several years ago, Schubert and his colleagues began to approach the treatment of Alzheimer’s from a new angle. Rather than target amyloid, the lab decided to focus 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. In all other cases, old age is the primary risk factor, said 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.
In the latest research three groups of rapidly aging mice included 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. Notably, 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 mice. These included markers for increased energy metabolism, reduced brain inflammation and reduced levels of oxidized fatty acids in the brain.
Another important effect was that J147 prevented the leakage of blood from the microvessels in the brains of old mice. “Damaged blood vessels are a common feature of aging in general, and in Alzheimer’s, it is frequently much worse,” said Currais.
Currais and Schubert hope to move J147 into human clinical trials for Alzheimer’s disease.
“If proven safe and effective for Alzheimer’s, the apparent anti-aging effect of J147 would be a welcome benefit,” added Schubert. The team aims to begin human trials next year.