New Drug Treats Bone Loss AND Diabetes

In a case of medical multitasking, researchers have developed a new class of drug candidates that can address bone loss as well as diabetes. The work was co-led by Patrick R. Griffin, Ph.D., a professor on the Florida campus of The Scripps Research Institute (TSRI), and B. Lecka-Czernik, Ph.D., a professor at the University of Toledo.

As indicated in the July 27, 2016 news release, the study “…has shown that a new class of drug candidates developed at TSRI increases bone mass by expanding bone formation (deposition of new bone) and bone turnover (a normal process of replacement of old bone). A proper balance of these two processes is critical to healthy bone maintenance), and this balance is frequently negatively affected in diabetic patients. The result is a new dual-targeting drug candidate—or, as Griffin describes, ‘one drug addressing multiple therapeutic indications’—that could treat both diabetes and bone disease. The compound has been referenced as SR10171.”

Dr. Griffin and TSRI Associate Professor Theodore Kamenecka, Ph.D. have done prior work on molecules that increase sensitivity to insulin. Their new drug candidates “target a receptor known as peroxisome proliferator-activated receptors gamma (PPARγ), a key regulator of stem cells controlling bone formation and bone resorption and a master regulator of fat. Anti-diabetic drugs known as glitazones (TZDs) target the PPARγ protein, but that interaction leads to severe bone loss and increased fractures. Stem cells in the bone marrow can differentiate either into bone cells or fat cells, and the glitazones drive them to fat at the expense of bone.”

“But SR10171 is designed to avoid this troubling outcome. In animal models treated with the compound, fat formation in the bone marrow was successfully blocked independent of their metabolic state (healthy or diabetic).”

“Using structural biology techniques and rational design synthetic chemistry, SR10171 was constructed to engage the PPARγ protein in a unique way possessing an optimal balance with the receptor’s other family member, PPARa, to treat diabetes and, at the same time, improve bone health, ” Dr. Griffin said. “This targeted polypharmacological approach demonstrates that the target isn’t the problem if you target it correctly.”

“SR10171 improves bone mass regardless of body mass index, normal to obese, ” Dr. Griffin added. “So you could use such a drug to treat osteoporosis whether patients are diabetic or not.”

Dr. Griffin told OTW, “While this compound has the potential to be used post-surgery to promote bone growth, its primary use would be as an adjuvant for current osteoporosis treatments. We expect to continue to study this compound and hope to eventually move it into clinical development.”