Scripps spotlights PPARγ inhibitor as a potential drug for bone loss

Scripps' Dr. Patrick Griffin

A team of scientists from The Scripps Research Institute led by Dr. Patrick Griffin has observed for the first time that a novel compound may help promote bone formation in patients afflicted with bone loss.

It's been shown before that reducing a protein known as the master regulator of fat--PPARγ--in a genetic mouse model spurs bone formation. Published in Nature Communications, his team showed this scientific rationale could be mimicked using an inhibitor of PPARγ. Using a novel compound which they named SR2595 to treat human mesenchymal stem cells, they observed a significant increase in osteoblasts--a cell type essential for the formation of bone.

Since mesenchymal stem cells can be 'forced' to adopt multiple cell types other than bone forming cells--such as fat, connective tissue and cartilage--their approach could be potentially important for treating other diseases as well.

Despite the fact that this preclinical work is preliminary, Griffin has his sights set on advancing the work toward the clinic. "We have already demonstrated SR2595 has suitable properties for testing in mice; the next step is to perform an in-depth analysis of the drug's efficacy in animal models of bone loss, aging, obesity and diabetes," he notes.

David Marciano, first author of the current study and a Ph.D. student in Griffin's lab, adds that "because PPARG is so closely related to several proteins with known roles in disease, we can potentially apply these structural insights to design new compounds for a variety of therapeutic applications." As such, understanding more about the PPAR-protein family may inspire new drug candidates for a range of diseases in the future.

- here's the release
- read the research abstract

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