Osteoactivin Treatment for Accelerating Spinal Fusion in Osteoporosis

Project Summary Abstract Overspinal fusions are performed annually in the US of whichundergo revision due to failure to fuseThe mean age for spinal fusion increased fromtoyears inIn patients older thanyearsthe frequency of osteoporosis is reported to bein women andin manThese patients experience substantial deterioration in the quality of lifeincreased dependency on othersand reduced lifespanVertebral interbody spinal fusion through osteoinductive therapy was developed to prevent or reduce much of this suffering and extend livesHoweverthe current therapy for thisBMPMedtronic Infusehas been shown to lead to significant inflammationbone cyst formationectopic bone formationnerve root injuryand cancerUnlike BMPOsteoactivinrOAa recombinant proteininduces bone fusion without inflammation or other complicationsPreliminary data shows that it can successfully regenerate bone and it was successful in Land Lspinal fusion in healthy male ratsRecentlya small peptide version of OAOA pwas discovered and shown to equivalently regenerate boneThis is exciting because a small peptide provides higher potency and targeting than a small molecule while maintaining a smaller size and decreases toxicity and accumulation potential than the whole proteinand so can be used repeatedly in the same individualThereforein this Phase I SBIR studywe propose to evaluate the commercial feasibility of OA p for spinal fusionspecifically by testing it in the ovariectomized osteoporotic ratIf successfulthis work will demonstrate the potential of OA p to be used as a novel osteoinductive therapy for accelerating spinal fusion without the complications associated with BMPand with potential extension to other applications Public Health Relevance Osteoporosis is a major health care problem since approximatelymillion people over the age ofhave been diagnosed with the disease andmillion more are estimated to have low bone massosteopeniaOsteoactivin is a novel protein in bone and the proposed studies will generate new information regarding its effects and mechanisms of action on bone cell development and functionOnce we understand its full effects on bone and how it works to promote bone formationthis information will be helpful in developing new therapeutic strategies to selectively enhance bone formation in patients with clinically significant bone loss