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The study of gene therapy for aseptic loosening using a mouse implant model

利用小鼠种植体模型进行无菌性松动基因治疗的研究

基本信息

批准号：
7748193
负责人：
SHANG-YOU YANG
金额：
$ 6.32万
依托单位：
VIA CHRISTI REGIONAL MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-06-15 至 2010-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7748193
关键词：
Adverse effects Adverse reactions Age Air Animal Model Animals Anti-Inflammatory Agents Anti-inflammatory Biomechanics Bone Resorption Bone Tissue Canis familiaris Cells Characteristics Clinical assessments Code Complication Data Dependovirus Effectiveness End Point Engineering Enzyme-Linked Immunosorbent Assay Evaluation Failure Fibroblasts Finite Element Analysis Foundations Future Gene Delivery Gene Transfer Gene Transfer Techniques Genes Goals Half-Life Head Histologic Histology Human Implant Incidence Inflammation Inflammatory Investigation Joint Prosthesis Joints Knee joint Lead Literature Longevity Mediating Modeling Molecular Molecular Biology Techniques Monitor Mus Operative Surgical Procedures Oryctolagus cuniculus Osteolysis Osteolytic Outcome Study Particulate Pathology Patients Principal Investigator Process Production Property Prosthesis Prosthesis Failure Publishing Range Replacement Arthroplasty Reporting Safety Scanning Screening procedure Shear Strength Sheep Site Testing Therapeutic Therapeutic Agents Therapeutic Effect Therapeutic Intervention Time Tissues Titanium Transgenes Treatment Protocols Tumor necrosis factor receptor 11b Virus Week Weight-Bearing state Work Yang adeno-associated viral vector anakinra base bone cellular engineering combination gene therapy compare effectiveness cytokine gene therapy in vivo infancy innovation migration mouse model novel osteoclastogenesis particle prevent programs response selective expression stem targeted delivery therapeutic protein therapeutic transgene tibia tool trafficking transgene expression tumorigenesis ultra-high molecular weight polyethylene vector

项目摘要

DESCRIPTION (provided by applicant): Aseptic loosening has become the major complication of total joint replacement, with an incidence of as high of 34%. Our long-term goal is to develop therapeutic approaches to prevent or retard the process of aseptic loosening of prosthetic joint. Our hypothesis is that wear debris-associated inflammation and osteolysis are separate but related mechanisms in the periprosthetic tissue, and both anti-inflammatory therapy and antiosteolytic therapy are required to inhibit aseptic loosening. Delivery of the generally short half-life therapeutic agents to the loosening prosthetic joint is highly problematic. Gene therapy, though still in its infancy, provides attractive avenue for targeted delivery and sustained expression of therapeutic protein(s). The objective of this proposal is to validate a murine long-term model of a prosthetic joint failure due to wear debris stimulation for the evaluation of combination gene therapy against inflammation and osteolysis. This will be accomplished by pursuing the following specific aims: (1) to characterize the biomechanical and pathological aspects of a longterm mouse model of debris-associated bone resorption and joint prosthesis failure; (2) to evaluate the efficacy of combination anti-inflammatory and anti-osteolytic gene therapy in preventing or treating debris-associated implant loosening; and (3) to examine the influence and cell trafficking of a cell-gene (ex vivo) therapy, and compare it with in vivo gene transfer on the aspects of transgene expression and dissemination, long-term effectiveness, and potential adverse effects. The successful outcome of the study will validate a useful tool for the investigation of aseptic loosening, and lay important foundations for virus-mediated gene delivery of therapeutic proteins, especially OPG in combination with pro-inflammatory cytokine blockers, as a promising therapeutic regimen for debris-associated prosthetic loosening.

描述（由申请人提供）：