A paper titled “A comprehensive multiomics approach toward understanding the relationship between aging and dementia” and published in the journal Aging by researchers from Salk Institute for Biological Studies suggests that J147, an experimental drug developed by the team for the treatment of Alzheimer’s disease is now effective for reversing the aging process.
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Although successful tests have been concluded on mice in lab settings, the researchers are now running further tests to determine if it will work on humans.
The properties of experimental drug J147 were unexpectedly discovered to have anti-aging effects on lab mice – their memory improved and their cognition soared, and the blood vessels in the brain of the mice got healthier even as the rats showed they are now capable of improved physiological capabilities.
“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 form of presenile dementia that is similar to senile dementia except that it usually starts in the 40s or 50s. Its first symptoms are impaired memory, and this is followed by impaired thought pattern and speech, and then complete helplessness and total reliance on others sets in on the patient.
Alzheimer’s is ranked the third leading cause of death in the US, affecting over 5 million Americans. The National Institutes of Health also revealed it is the leading cause of dementia among the older population.
The hallmark of the disease is the amyloid plaque deposits found in the brain of patients, and most drugs have been designed to target the plaque, but their effects in real-life situations have not been satisfying, even though they worked great on mice in lab settings.
Schubert and his colleagues decided to tackle the disease from another angle, and instead of targeting amyloid plaques like other researchers have been doing, the team came in from the angle of old age which is a major risk factor for Alzheimer’s. The Salk team used cell-based screens against old age related brain toxicities, and then synthesized J147 on this basis.
The researchers understand that old age is the precursor to having Alzheimer’s disease, and they also understand that genes in the brain together with over 500 different molecules linked to metabolism are associated with the development and effects of the disease, so they went back to lab mice to express these differences and then alter the experiments to reflect their theories.
“Damaged blood vessels are a common feature of aging in general, and in Alzheimer's, it is frequently much worse,” Currais said after noting that J147 prevented blood leaking from the microvessels of old lab mice; and the team thinks it is high time real patients are tested with the drug candidate to validate results obtained with lab mice.
“If proven safe and effective for Alzheimer’s, the apparent anti-aging effect of J147 would be a welcome benefit,” adds Schubert. The team aims to begin human trials next year.
Abrexa Pharmaceuticals have been issued license to produce J147 by Salk Institute after receiving patent for it.
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Other researchers involved with the study are Oswald Quehenberger of the University of California, San Diego; and Joshua Goldberg, Catherine Farrokhi, Max Chang, Marguerite Prior, Richard Dargusch, Daniel Daugherty and Pamela Maher of the Salk Institute.