Boston, Massachusetts (PressExposure) August 11, 2009 -- Guo-Ping Shi, a biochemist from the Department of Medicine at BWH, began to suspect such a connection when, in a previous study, he found mast cells present in a variety of inflammatory vascular diseases.
Mast cells are immune cells that facilitate healing in wounded tissue, primarily by increasing blood flow to the site. However, in certain conditions mast cells build up to levels far beyond what the body needs. As a result these cells become unstable and eventually, like punctured trash bags, leak molecular "garbage" into the tissue. This can result in chronic inflammation that causes asthma and certain allergies.
As Shi and colleagues discovered, mast cells were far more abundant in fat tissue from obese and diabetic humans and mice than they were in normal weight fat tissue. This led to an obvious question: by regulating mast cells, could we then control the symptoms?
To find out, Shi and colleagues took a group of obese and diabetic mice and, for a period of two months, treated them with either ketotifen fumarate (also called Zaditor) or cromolyn, both over-the-counter allergy drugs.
"We knew from published research that both cromolyn and Zaditor help stabilize mast cells in people suffering from allergy or asthma," said Shi. "It's almost as if the drugs place an extra layer of plastic on the ripped trash bag. So it seemed like a logical place to begin."
The mice were divided into four groups. The first was the control group; the second group was simply switched to a healthy diet; the third was given cromolyn or ketotifen fumarate; and the fourth was both given the drug and switched to a healthy diet.
While symptoms of the second group improved moderately, the third group demonstrated dramatic improvements in both body weight and diabetes. The fourth group exhibited nearly 100 percent recovery in all areas.
To bolster these findings, Shi and colleagues then took a group of mice whose ability to produce mast cells was genetically impaired. Despite three months of a diet rich in sugar and fat, these mice neither became obese nor developed diabetes.
"The best thing about these drugs is that we know it's safe for people," says Shi. "The remaining question now is: Will this also work for people?"
Shi now intends to test cromolyn and ketotifen fumarate on obese and diabetic non-human primates.
The research was funded by grants from the National Institutes of Health.