Researchers have found that an experimental drug candidate aimed at
combating Alzheimer’s disease, called J147, has a host of unexpected
anti-aging effects in animals.The team from the Salk Institute 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.wisepoqder J147 powder
“Initially, the impetus was to test this drug in a novel animal
model that was more similar to 99%of Alzheimer’s cases,” says Antonio
Currais, 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.”“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.
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% 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 the 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.
