Scientists have finally cracked the code of how an experimental new drug called J147, which has a proven track record of reversing Alzheimer’s disease in mice, turns back the clock in cells, making them appear more youthful. The new discovery is a crucial step in readying the drug for human studies.
In a paper published on January 7, 2018 in the journal Aging Cell, researchers from Salk Institute for Biological Studies reported previously unknown details about how the drug, made from a modified version of a molecule found in curcumin, works in the brain. They found it binds to a protein in mitochondria, the cells responsible for generating energy. In doing so, it makes cells appear younger—at least in the mice the drug has been tested on so far.
“This really glues together everything we know about J147 in terms of the link between aging and Alzheimer’s,” said Dave Schubert, head of Salk’s Cellular Neurobiology Laboratory. “Finding the target of J147 was also absolutely critical in terms of moving forward with clinical trials.”
J147 was first developed in 2011, and researchers have carried out several studies that show it can reverse memory loss and slow or reverse Alzheimer’s in mice. But until this study, they didn’t know how it worked within cells. They were able to show that J147 works by manipulating ATP, a protein in the mitochondria and the body’s mobile source of energy. When J147 was present, neurons were protected from toxicities associated with aging. Additional experiments showed that J147 increases the levels of ATP and promotes healthier, more stable mitochondria.
“We know that age is the single greatest contributing factor to Alzheimer’s, so it is not surprising that we found a drug target that’s also been implicated in aging,” said Josh Goldberg, the paper’s first author.
Scientists have long targeted the protein beta-amyloid, which accumulates in the brains of Alzheimer’s patients, but since age is the single biggest risk factor for dementia, a drug that targets it could be the piece of the puzzle researchers have been looking for. J147 could potentially be successful in other neurodegenerative diseases, too, like Parkinson’s. “People have always thought that you need separate drugs for Alzheimer’s, Parkinson’s and stroke,” said Schubert. “But it may be that by targeting aging we can treat or slow down many pathological conditions that are old-age associated.”
This study was published in the journal Aging Cell.