Use of bone morphogenetic protein-9 gene therapy to induce spinal arthrodesis in the rodent

Object. Bone morphogenetic proteins (BMPs) have been shown to have signific ant osteoinductive activity in numerous in vitro and in vivo assay systems, and BMP-2 and BMP-7 are currently being evaluated in human clinical studie s. In the spinal region, BMPs have been shown to promote spinal arthrodesis at a higher rate than autologous bone alone. The delivery of BMPs via dire ct or ex vivo gene therapy techniques is also currently being evaluated and has shown promise in several mammalian models. The present study was desig ned to evaluate the efficacy of the use of direct, percutaneous BMP-9 adeno viral gene therapy to promote spinal fusion in the rodent. Methods. Each animal was injected with 7.5 x 10(8) pfu of a BMP-9 adenovira l vector in the lumbar paraspinal musculature and allowed to survive 16 wee ks. Computerized tomography studies and histological analysis demonstrated massive bone induction at the injection sites, clearly leading to solid spi nal arthrodesis, without evidence of pseudarthroses, nerve root compression , or systemic side effects. Conclusions. The results of this study strongly support the advancement of BMP gene therapy techniques toward clinical use.