Percutaneous spinal fusion using bone morphogenetic protein-2 gene therapy

Object. Gene therapy has many potential applications in neurosurgery. One a pplication involves bone morpho genetic protein-2 (BMP-2), a low-molecular- weight glycoprotein that induces bone formation in vivo. Numerous studies h ave demonstrated that the BMP-2 protein can enhance spinal fusion. This stu dy was undertaken to determine whether direct injection of an adenoviral co nstruct containing the BMP-2 gene can be used for spinal fusion. Methods. Twelve athymic nude rats were used in this study. Recombinant, rep lication-defective type 5 adenovirus with the cytomegalovirus (CMV) promote r and BMP-2 gene (Ad-BMP-2) was used. A second adenovirus constructed with the CMV promoter and beta-galactosidase (beta-gal) gene (Ad-P-gal) was used as a control. In three groups (four rats each) 7.5 mu l of virus (5 x 10(8 ) particles/mu l) was injected percutaneously and paraspinally at the lumbo sacral junction: Group 1 received Ad-BMP-2 bilaterally; Group 2 received Ad -BMP-2 on the right, Ad-beta-gal on the left; and Group 3 received Ad-beta- gal bilaterally. Computerized tomography (CT) scans of the lumbosacral spin e were obtained at 3, 5, 8, and 12 weeks. At 12 weeks, the animals were kil led and underwent histological inspection. Ectopic bone formation was obser ved both on three-dimensionally reconstructed CT scans and histological exa mination in all rats at sites treated with Ad-BMP-2. Histological analysis demonstrated bone at different stages of maturity adjacent to the spinous p rocesses, laminae, and transverse processes. Conclusions. Results of this study clearly demonstrated that it is possible to produce in vivo endochondral bone formation by using direct adenoviral construct injection into the paraspinal musculature, which suggests that ge ne therapy may be useful for spinal fusion in the future.