Salk team finds molecule that slows the clock on key aspects of aging in animals
Salk Institute researchers have found that an experimental drug candidate aimed at combating Alzheimer’s disease has a host of unexpected anti-aging effects in animals.
The Salk team 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.
In this latest work, 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. The 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. 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 young animals. These included markers for increased energy metabolism, reduced brain inflammation and reduced levels of oxidized fatty acids in the brain.
Another notable 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,” says Currais.
Currais and Schubert note that while these studies represent a new and exciting approach to Alzheimer’s drug discovery and animal testing in the context of aging, the only way to demonstrate the clinical relevance of the work is 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,” adds Schubert. The team aims to begin human trials next year.
The Latest on: J147
via Google News
The Latest on: J147
- New Drug Stops Alzheimer’s — in Miceon August 7, 2018 at 5:00 pm
The study is published in the journal PLoS One. “J147 enhances memory in both normal and Alzheimer’s mice and also protects the brain from the loss of synaptic connections,” said David Schubert, Ph.D.
- Promising Alzheimer’s Drug Nearing Clinical Trialson February 9, 2018 at 4:00 pm
J147, the molecular targeting drug, has been shown to treat Alzheimer’s disease and reverse aging in mice is nearing readiness for the clinical trials in humans. Scientists have been able to determine ...
- Alzheimer’s drug turns back clock in powerhouse of cellon January 8, 2018 at 4:00 pm
Salk Institute for Biological Studies. (2018, January 9). Alzheimer’s drug turns back clock in powerhouse of cell: Researchers identify molecular target of J147, which is nearing clinical trials to ...
- How a promising Alzheimer's drug turns back the cellular clockon January 8, 2018 at 4:00 pm
A drug dubbed J147, developed by the Salk Institute, is one of the most promising candidates to treat Alzheimer's, but just how it worked at the molecular level remained a mystery. Now Salk scientists ...
- Researchers identify the molecular target of J147, which is nearing clinical trials to treat Alzheimer's diseaseon January 8, 2018 at 4:00 pm
The experimental drug J147 is something of a modern elixir of life; it's been shown to treat Alzheimer's disease and reverse aging in mice and is almost ready for clinical trials in humans. Now, Salk ...
- Experimental drug targeting Alzheimer's disease shows anti-aging effectson November 13, 2015 at 2:47 am
Scientists have discovered a molecule that slows the clock on key aspects of aging in animals. Salk Institute researchers have found that an experimental drug candidate aimed at combating Alzheimer's ...
- Experimental drug targeting Alzheimer's disease shows anti-aging effectson November 11, 2015 at 4:00 pm
Salk Institute researchers have found that an experimental drug candidate aimed at combating Alzheimer's disease has a host of unexpected anti-aging effects in animals. The Salk team expanded upon ...
- Possible Alzheimer’s drug cut mice aging symptomson November 11, 2015 at 4:00 pm
The study examined the effects of the drug, J147, in a strain of mice bred to rapidly age and show signs of senescence. It is the second mouse model to show effectiveness. Besides improved cognition ...
- Salk Researchers Halt The Progression Of Alzheimer’s In Very Old Miceon May 13, 2013 at 5:00 pm
Researchers at the Salk Institute are making progress on a compound that they believe could potentially stop Alzheimer's disease in its tracks. To show just how promising their drug candidate is, they ...
- J147 Reverses Memory Deficits In Mice With Alzheimer's Diseaseon May 13, 2013 at 5:00 pm
The drug candidate J147 was able to reverse memory deficits and improve several aspects of brain function in mice with advanced symptoms of Alzheimer's disease, according to a new study. Previous ...
via Bing News