Percutaneous spinal fusion using bone morphogenetic protein-2 gene therapy.
OBJECTIVE
Gene therapy has many potential applications in neurosurgery. One application involves bone morphogenetic protein-2 (BMP-2), a low-molecular-weight glycoprotein that induces bone formation in vivo. Numerous studies have demonstrated that the BMP-2 protein can enhance spinal fusion. This study was undertaken to determine whether direct injection of an adenoviral construct containing the BMP-2 gene can be used for spinal fusion.


METHODS
Twelve athymic nude rats were used in this study. Recombinant, replication-defective type 5 adenovirus with the cytomegalovirus (CMV) promoter and BMP-2 gene (Ad-BMP-2) was used. A second adenovirus constructed with the CMV promoter and beta-galactosidase (beta-gal) gene (Ad-beta-gal) was used as a control. In three groups (four rats each) 7.5 microl of virus (5x10(8) particles/microl) was injected percutaneously and paraspinally at the lumbosacral 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 spine were obtained at 3, 5, 8, and 12 weeks. At 12 weeks, the animals were killed and underwent histological inspection. Ectopic bone formation was observed both on three-dimensionally reconstructed CT scans and histological examination in all rats at sites treated with Ad-BMP-2. Histological analysis demonstrated bone at different stages of maturity adjacent to the spinous processes, 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 gene therapy may be useful for spinal fusion in the future.
Department of Neurosurgery, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
T D
TD
Alden
D D
DD
Pittman
E J
EJ
Beres
G R
GR
Hankins
D F
DF
Kallmes
B M
BM
Wisotsky
K M
KM
Kerns
G A
GA
Helm
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics* / Q000627:therapeutic use; D003587:Cytomegalovirus / Q000235:genetics*; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D010012:Osteogenesis; D011401:Promoter Regions, Genetic; D051381:Rats; D011923:Rats, Nude; D011994:Recombinant Proteins / Q000235:genetics; D013123:Spinal Fusion / Q000379:methods*; D013131:Spine / Q000254:growth & development / Q000473:pathology; D016212:Transforming Growth Factor beta
C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta