Combined Gene Therapy/Tissue Engineered Cartilage Repair

描述（来自申请人）：本I期协议的目标

DESCRIPTION (Verbatim from Applicant): The objective of this Phase I protocol is to develop a novel approach for the repair of articular cartilage using gene enhanced tissue engineering (GETE). Successful clinical repair of articular cartilage continues to be elusive. The current study seeks to repair articular cartilage defects using constructs containing cultured periosteal cells transduced with IGF-l (insulin-like growth factor) and BMP-7 (bone morphogenic protein) genes as a bilayer implant. As growth factors with strong chondrogenic (IGF-l) and osteogenic (BMP-7) properties, these growth factors have good potential in the healing of osteochondral defects. Tissue constructs have been developed which deliver progenitor cells transduced with IGF-l and BMP-7 genes. Further development of the technology and efficacy will be evaluated in a series of in vivo tests using a lapine knee defect model. These studies will focus on the testing of an improved, safe, and reproducible approach to the repair of joint surfaces. The research design methods to develop the technology are as follows: 1) Construction of a retroviral expression system for delivery of IGF-l and BMP.7 genes. 2) Evaluation of GETE matrices as delivery vehicles for IGF-l and BMP-7 genes. 3) Evaluation of the cartilage reparative capacity using the GETE technology. The parameters for evaluating cartilage repair include: a) Collagen typing as compared to normal cartilage, b) Biochemical measurements of GAG, collagen, and water content within the repaired cartilage tissue, c) Histological characterization of the repaired cartilage, and d) Material properties compared to normal cartilage with respect to modulus and permeability. Further refinements will be the subject of a Phase Il study, which would evaluate this GETE technology in the repair of knee articular cartilage defects in a large animal (sheep) weight bearing joint model. This novel approach using GETE technology should further expand our knowledge of cartilage tissue repair and may have important clinical applications in the future. PROPOSED COMMERCIAL APPLICATION: There is no currently reliable and consistent method used for the repair of articular cartilage. The estimated market for such a device based on approximately 500,000 cases of arthroscopic surgery for damaged cartilage done per year with a price of about $2,000 per implant would mean a market size of 1.05 billion dollars a year for the U.S. market alone.