Bone forming therapeutic for use in spinal fusion devices and treatment of systemic bone diseases and disorders.
Millions of bone grafting procedures are performed worldwide each year. In spinal fusions the bone healing failure rate may be as high as 40%. The iliac crest is often used as a donor site for autologous grafts but there are many complications that can develop from this type of bone graft harvesting including pain, nerve damage, and hematoma. There is also limited supply of iliac bone as well as substantial cost associated with this surgery. Bone morphogentic proteins (BMP) are being used increasingly in orthopedic surgeries. These small molecules are capable of inducing new bone formation when delivered in the appropriate concentration and on the appropriate scaffold and do not require harvesting bone from remote sites of the patient. The FDA has approved several devices including INFUSETM which is used in spinal surgeries. The high cost and need for high concentrations of BMP create barriers for routine clinical use so there is a need for other compounds that can substitute or complement the use of BMPs.
Cellular response to BMPs depends on intracellular signaling pathways involving proteins called Smads. The baseline level of Smads is in part affected by their ability to interact with another protein, Smurf1. Smurf1 interacts with Smad1/5 and targets them for degradation leading to reduced BMP signaling. Therefore, therapeutics that modulate the effects of Smurf1 may have the potential to replace or complement BMP. Emory researchers have identified compounds that interact with Smurf1. These compounds potentiate the effects of BMP-2 and induce osteoblastic differentiation of C2C12 myoblasts in vitro in a dose dependent manner. Emory investigators have identified a lead compound, SVAK-12X, which is a major metabolite of an FDA-approved anti-microbial drug currently on the market.
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