by Arlene Weintraub |
Jul 5, 2017 12:00pm
The anti-inflammatory drug amlexanox was
invented in Japan in the 1980s to treat asthma but was quickly eclipsed by more
effective treatments. Now a team of scientists led by the University of
California at San Diego is looking at repurposing the drug in an entirely new
setting: Type 2 diabetes.
The UCSD team, working with scientists at the
Salk Institute and the University of Michigan, discovered that two enzymes called
IKKε and TBK1 are ratcheted up in obese mice, making it difficult for them to
burn calories and expend energy. So they screened 150,000 chemicals in search
of something that would inhibit those two enzymes, according to a press release
from UCSD. That’s when they stumbled upon amlexanox. They’ve now shown that
some people with Type 2 diabetes experience a significant drop in glucose after
taking the drug.
The researchers tested amlexanox in 21 people
with obesity and Type 2 diabetes, and compared them to a control group given a
placebo. A third of people taking the drug responded to it, according to the
release.
Patients who had nonalcoholic fatty liver disease also responded well
to it.
The researchers wanted to understand what
separated the responders from the non-responders, so they took biopsies of fat
cells from the patients at the beginning and end of the study. They discovered
more than 1,100 genetic changes that occurred in people who responded to
amlexanox, but that were absent in patients who didn’t respond.
The link to inflammation was also evident in
those biopsies. "In the responder group, the level of inflammation in fat
was higher than in the non-responder group at the beginning of the study,
indicating that there is something about inflammation that predisposes a person
to respond,” said Alan Saltiel, Ph.D., director of the UC San Diego Institute
for Diabetes and Metabolic Health, in the release. The findings were published
in the journal Cell Metabolism.
The UCSD-led project is among many aimed at
finding new targets for treating metabolic disorders. Another approach that has
been gaining steam lately involves turning unhealthy white fat into brown
adipocytes—cells that burn energy and seem to fend off obesity. Last year,
scientists at the University of Pennsylvania announced they had identified a signaling pathway that
converts white fat to brown fat and might be able to be targeted with drugs.
Inhibiting inflammatory enzymes is an entirely
new approach, UCSD’s Saltiel acknowledges, and it raises several challenges
that still need to be addressed. His team is now working to figure out which of
the thousands of gene changes are most important to address, what the proper
dosage of amlexanox should be in people with diabetes and related disorders,
and what other drugs might be able to be used in combination with the asthma
treatment to make it more effective.
"It's a new mechanism for a diabetes and
fatty liver drug,” Saltiel said. “It's promising, but there are a lot of
questions that need to be answered still."
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