Over 450,000 lumbar spine fusions are performed each year in the US, which result from a number of spinal pathologies that include degenerative lumbar slips, lumbar stenosis, degenerative scoliosis and fractures. In the US, an aging population, high smoking rates, increasing obesity, and longer life expectancy together will increase the number of lumbar spinal fusion procedures by 100% over the next decade. Successful lumbar fusion has been associated with improved outcomes in patient qualify of life. Conversely, diminished healing results in increased morbidity and decreased quality of life for the patient. Moreover, the burden to the healthcare system for a failed lumbar spine fusion procedure increases the overall cost substantially. Specifically, an extra $80,000 is spent per patient for a lumbar non-union surgery resulting in over $7 billion per year spent on treating these patients. Treatment options that promote fusions are limited, with only a few treatment modalities available to clinicians. In addition, newer treatment modalities based on biologic growth factors have had a number of significant drawbacks including increased cancer risk and a 44% surgical revision rate. In response to this unmet need, Fusologics, LLC, a regenerative medicine company based in Syracuse, New York, is commercializing ZetaFuseâ¢, a novel surgical implant with proven ability to promote bone growth by activating a novel molecular pathway in mesenchymal stem cells. Based on the discovery of a novel mechanism of action to induce bone growth, ZetaFuse drives osteogenesis via the local administration of an implant that contains a small molecule drug combined with a collagen and calcium ceramic composite carrier. In addition, ZetaFuse⢠leverages components with well-established clinical safety profiles. If validated, ZetaFuse⢠would empower clinicians with a with a safe and effective tool to promote bone formation and enable successful and cost-effective lumbar fusion procedures absent the significant drawbacks of current therapies for a growing patient population. In this Phase I proposal, we will build on the successful results of our rabbit posterolateral fusion study, which demonstrated proof-of-concept with a research prototype of ZetaFuse, to generate and validate a commercial-grade prototype of ZetaFuse as a viable local bone growth therapy for patients requiring lumbar spine fusion procedures. This proposal consists of two AIMs: 1) optimization of the ZetaFuse osteogenic carrier, and 2) validation of the ZetaFuse implant in relevant in vivo studies. If successful, this proposal will demonstrate commercial proof-of-concept for the ZetaFuse implant and establish the foundation for a Phase II proposal to support remaining preclinical development in preparation for human trials.
Public Health Relevance Statement: Project Narrative Bone growth is critical to a favorable fusion rate and good prognosis in the 450,000 patients who undergo lumbar spine fusion procedures to treat degenerating discs, spondylolisthesis, lumbar stenosis and scoliosis. Over the next decade, as the aging US population grows, the number of lumbar spine fusion surgeries performed yearly is estimated to increase by 100%, which means that there is an urgent need for technology that can safely create new bone leading to a successful fusion. The current treatment options are limited and fraught with complications that result in poor patient outcomes and an increase healthcare expenditures. In response to this unmet need, Fusologics, LLC, a New York-based regenerative medicine company, is commercializing ZetaFuseâ¢, a novel surgical implant that has demonstrated the ability to promote bone growth by activating a novel molecular pathway using components with well-established clinical safety profiles.
Project Terms: Aging; aging population; allogenic bone transplantation; animal data; Animals; Anterior; Autologous Transplantation; base; Binding; Biocompatible Materials; Biological; Biological Response Modifier Therapy; bone; Bone callus; bone cell; Bone Growth; Bone Marrow Cells; bone morphogenic protein; Bone Transplantation; Cadaver; Calcium; cancer risk; Cellular Assay; Ceramics; Clinical; cohesion; Collagen; commercialization; Comorbidity; cost; cost effective; Diffusion; Dose; efficacy testing; experimental study; Formulation; Foundations; Fracture; Growth Factor; Harvest; healing; Health Expenditures; Healthcare Systems; Human; Image; Implant; improved outcome; in vivo; inhibitor/antagonist; Kinetics; Life; Life Expectancy; Marrow; Mechanics; Mediating; Mesenchymal Stem Cells; methionine-enkephalin receptor; Modality; Modeling; Molecular; monocyte; Morbidity - disease rate; Naloxone; neoplastic cell; New York; novel; Obesity; Operative Surgical Procedures; Opioid; Orthopedics; Oryctolagus cuniculus; Osteoblasts; Osteoclasts; Osteogenesis; osteogenic; outcome forecast; Pathology; Pathway interactions; patient population; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Phase; Population; preclinical development; Preparation; Procedures; Property; prototype; PTH gene; Quality of life; Regenerative Medicine; Research; response; Safety; sarcoma; scoliosis; Second Look Surgery; Site; small molecule; Smoking; Spinal; Spinal Fusion; Spondylolisthesis; stem cell differentiation; Stenosis; Technology; Testing; Therapeutic; Time; tool; tumor growth; Validation; Vertebral colum
