MEND researchers are ready for human trials of an obesity drug showing dramatic results in mice

June 28, 2013, University of Michigan
In Dr. Alan Saltiel's study at U-M, both mice above were fed a high-fat diet. The mouse on the left is a normal weight after receiving amlexanox. Credit: Shannon Reilly

As sometimes happens in science, a medication used for one thing turns out to be very good for something else.

Such appears to be the case with the drug amlexanox, an and canker sore medication, which has been shown by U-M researcher Dr. Alan Saltiel to inhibit two genes that play a role in and fat-burning in mice. And it may have the same effect on humans, potentially improving , insulin resistance, obesity, and non-alcoholic (NAFLD).

Now the time has come to test the drug's effectiveness in humans. Elif Oral, M.D., Associate Professor of Internal Medicine in the Division of Metabolism, Endocrinology & Diabetes (MEND), is seeking people with type 2 diabetes or obesity and evidence of central obesity (belly fat) for this potentially ground-breaking study using amlexanox in humans. People can be on oral diabetes medication (no insulin) and should have a Body Mass Index (BMI) between 27 and 36 and an Hb A1c of less than 9.5%.

Since this is a "proof-of-concept" study in the early stages of this investigation, only 10 participants are needed. All test and drug costs are covered by the study and, in addition, the subjects will be compensated for their time.

If the drug is shown to work in humans, according to Dr. Oral, "This would mean that there is a completely different drug available for people that has a completely different mechanism of action in the body. If this drug can address weight and diabetes — as well as inflammation — without causing major side effects, this would be a huge innovation!"

Dr. Oral is also the director of the MEND Post-Bariatric Surgery Clinic and director of the U-M Health System's Bariatric Surgery Program and is an internationally recognized expert on lipodystrophy (a disorder of the fat cell hormone called leptin). Through her clinical practice at the MEND Clinic and her role in the Bariatric Surgery Program, she has seen first-hand the toll that and diabetes take on people.

How did the idea to study amlexanox for such an off-label use come about? The lab of Dr. Alan Saltiel, Mary Sue Coleman Director of the U-M Life Sciences Institute (LSI), discovered that the genes IKKE and TBK1 play a crucial role for maintaining metabolic balance, first published in 2009 in the journal Cell.

Following this discovery, they searched for compounds that inhibit IKKE and TBK1, using high-throughput chemical screening at LSI's Center for Chemical Genomics. In this way, the researchers found the approved off-patent drug, amlexanox.

The Saltiel team then demonstrated that amlexanox had profound beneficial effects in both genetic and dietary-induced obese mice. The chemical lowered the weight of obese mice and reversed related metabolic problems such as and fatty liver. These findings were published this past February in the journal Nature Medicine.

Once the mouse findings were completed, Drs. Saltiel and Oral teamed up to translate these studies of amlexanox to humans in this clinical trial.

What's next? "After this first study," said Dr. Oral, "we will undertake a larger, simpler placebo-controlled trial and go after the effects that we will observe in the first study. I hope that this second study will start before the end of the year."

For the initial study, amlexanox is taken orally in a pill three times a day for a period of 12 weeks, followed by a follow-up four weeks after therapy ends. The researchers will evaluate the changes in metabolic parameters (e.g., blood cholesterol, liver function, ) and body composition characteristics (e.g., the pattern of fat distribution in the body). Seven eligible subjects in this study will also be evaluated for a change in liver disease by undergoing a liver biopsy, if they so wish.

Explore further: Old drug may point the way to new treatments for diabetes and obesity

More information: "Clinical Protocol to Investigate the Efficacy of Amlexanox for Treatment of Glucose and Lipid Abnormalities in Obese Type 2 Diabetes"

Related Stories

Old drug may point the way to new treatments for diabetes and obesity

February 10, 2013
Researchers at the University of Michigan's Life Sciences Institute have found that amlexanox, an off-patent drug currently prescribed for the treatment of asthma and other uses, also reverses obesity, diabetes and fatty ...

White blood cell enzyme contributes to inflammation and obesity

April 2, 2013
Many recent studies have suggested that obesity is associated with chronic inflammation in fat tissues. Researchers at Sanford-Burnham Medical Research Institute (Sanford-Burnham) have discovered that an imbalance between ...

Exercise benefits patients with type 2 diabetes

June 25, 2013
Moderate-intensity exercise reduces fat stored around the heart, in the liver and in the abdomen of people with type 2 diabetes mellitus, even in the absence of any changes in diet, according to a new study published online ...

Liver disease may raise risk of heart problems, study says

June 24, 2013
(HealthDay)—A new study adds to growing evidence of a link between a common liver disease associated with obesity and high risk for heart disease.

Cocoa may help fight obesity-related inflammation

June 12, 2013
(Medical Xpress)—A few cups of hot cocoa may not only fight off the chill of a winter's day, but they could also help obese people better control inflammation-related diseases, such as diabetes, according to Penn State ...

Discovery of new hormone opens doors to new type 2 diabetes treatments

May 7, 2013
Harvard School of Public Health (HSPH) researchers have discovered that a particular type of protein (hormone) found in fat cells helps regulate how glucose (blood sugar) is controlled and metabolized (used for energy) in ...

Recommended for you

Bioengineered soft microfibers improve T-cell production

January 18, 2018
T cells play a key role in the body's immune response against pathogens. As a new class of therapeutic approaches, T cells are being harnessed to fight cancer, promising more precise, longer-lasting mitigation than traditional, ...

Weight flux alters molecular profile, study finds

January 17, 2018
The human body undergoes dramatic changes during even short periods of weight gain and loss, according to a study led by researchers at the Stanford University School of Medicine.

Secrets of longevity protein revealed in new study

January 17, 2018
Named after the Greek goddess who spun the thread of life, Klotho proteins play an important role in the regulation of longevity and metabolism. In a recent Yale-led study, researchers revealed the three-dimensional structure ...

The HLF gene protects blood stem cells by maintaining them in a resting state

January 17, 2018
The HLF gene is necessary for maintaining blood stem cells in a resting state, which is crucial for ensuring normal blood production. This has been shown by a new research study from Lund University in Sweden published in ...

Magnetically applied MicroRNAs could one day help relieve constipation

January 17, 2018
Constipation is an underestimated and debilitating medical issue related to the opioid epidemic. As a growing concern, researchers look to new tools to help patients with this side effect of opioid use and aging.

Researchers devise decoy molecule to block pain where it starts

January 16, 2018
For anyone who has accidentally injured themselves, Dr. Zachary Campbell not only sympathizes, he's developing new ways to blunt pain.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.