A protein known as “PPARy” just may help develop new bone-forming cells in patients who are losing bone. Researchers from the Florida campus of The Scripps Research Institute (TSRI) have created a novel approach that focused on the protein’s impact on stem cells derived from bone marrow. This work has just been published in Nature Communications.
Study: New Approach to Developing Bone-Forming Cells
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According to the June 12, 2015 news release, “The scientists knew that a partial loss of PPARy in a genetically modified mouse model led to increased bone formation. To see if they could mimic that effect using a drug candidate, the researchers combined a variety of structural biology approaches to rationally design a new compound that could repress the biological activity of PPARy. The results showed that when human mesenchymal stem cells were treated with the new compound, which they called SR2595 (SR=Scripps Research), there was a statistically significant increase in osteoblast formation, a cell type known to form bone.”
“These findings demonstrate for the first time a new therapeutic application for drugs targeting PPARy, which has been the focus of efforts to develop insulin sensitizers to treat type 2 diabetes, ” said Patrick Griffin, Ph.D., chair of the Department of Molecular Therapeutics and director of the Translational Research Institute at Scripps Florida. “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.”
Dr. Griffin told OTW, “We expected our compounds to be neutral on bone or perhaps slightly positive on bone, but the effects are much more pronounced. We see a clear impact on bone turnover and bone density.”
“We have a new manuscript under review at a high impact journal that shows the positive effects on bone in obese mice. Because it takes a long time from submission to acceptance the animal work has been completed already—and we are very excited indeed.”
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This is a fascinating development. In my practice we've seen similar outcomes with the revised protocol. The key differentiator seems to be patient selection criteria. Has anyone else noticed the correlation with BMI thresholds?
Great point. I'd push back slightly on the conclusion, the sample size in the cited study is too small to draw population-level inferences. That said, the directional signal is compelling and worth a larger RCT.
We implemented a similar approach last year. Early results are promising but we're still gathering 12-month follow-up data. Happy to share our protocol if anyone is interested.
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