Scientists Awarded $2.5 Million Collaborative Grant to Develop New Diabetes Treatment

Patrick R. Griffin, co-chair of the Department of Molecular Medicine on the Florida campus of The Scripps Research Institute (TSRI), has been awarded a $2.5 million collaborative grant with Brigham and Women’s Hospital by the National Institute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health (NIH).

The new five-year study seeks to confirm whether the inhibition of a particular protein that plays a role in regulating the body’s response to fat might be a viable target in the treatment of type 2 diabetes.

Griffin and Jorge Plutzky, MD, from Brigham and Women’s Hospital in Boston are co-principal investigators for the five-year multi-PI grant. TSRI’s Theodore Kamenecka, an associate professor in the Department of Molecular Medicine, is a co-investigator on the study.

“This new grant will let us focus on several lead candidates that inhibit a particular protein to confirm that this is a potential target to treat type 2 diabetes,” Griffin said. “These lead compounds came from a high-throughput screen run at Scripps Florida. Our strong preliminary evidence supports the idea of targeting fat directly.”

Griffin’s work covers a wide area of diseases ranging from cancer to diabetes to age-related bone loss. But they are all characterized by their impact on human metabolism – and the galaxy of disorders that more often than not occur in clusters: obesity, abnormal cholesterol, high blood pressure and insulin resistance.

“What we are looking for – what we’ve always looked for – is using chemical biology approaches to create novel therapeutics for the treatment of metabolic disease,” Griffin said. “Our research efforts often complement others because in many metabolic syndromes, like obesity and diabetes, for example, the underlying aspects of the disorders overlap.”

What makes the new grant significant – and something of a milestone – is that Griffin now has five similar grants running simultaneously, several in collaboration with other institutes.

“Four of the five are highly collaborative, something we’re very good at – both within TSRI and with other research organizations,” he said. “It’s been one of the hallmarks of our research program.”

The latest study with Brigham and Women’s Health will focus on what is known as brown adipose tissue or brown fat, which serves as a kind of molecular furnace in humans, generating heat by burning large numbers of fat calories. Brown fat is loaded with mitochondria, the cell’s energy plant, which contain iron and give the fat its red-brown tint; mitochondria use nutrients to produce energy for the cell.

Brown fat is different than white adipose tissue (WAT), which stores energy and can lead to obesity. Studies have shown that brown fat characteristics can be induced in white fat through the inhibition of the protein retinaldehyde dehydrogenase 1 (ALDH1a1), which in turn protects against diet-induced obesity and diabetes.

The number of the grant is 1R01DK107239-01A1.