The use of bone morphogenetic protein-6 gene therapy for percutaneous spinal fusion in rabbits.
OBJECTIVE
Fusion procedures in the lumbar spine have been performed in the US since 1911. Since that time, the indications and techniques for spinal fusion have evolved. Despite technical advancements, spinal fusion remains a major operation, and fusion nonunion rates of up to 35% are still reported. In this study, the authors were able to induce intertransverse process fusions in immune-competent New Zealand White rabbits by percutaneous administration of an adenoviral vector containing the bone morphogenetic protein (BMP-6) gene (Ad-BMP-6). The results represent an important step forward in finding new methods to increase the success and decrease the morbidity associated with spinal fusion.


METHODS
Five New Zealand White rabbits were used. Injection of the adenoviral construct was performed at multiple levels (bilaterally) in each animal while using fluoroscopic guidance. Injection consisted of either Ad-BMP-6 or Ad-beta-galactosidase (beta-gal) (control). Because multiple levels were injected, each animal served as an internal control. The animals underwent postinjection computerized tomography (CT) scanning at 7 and 14 weeks. After undergoing final CT scanning, the animals were killed and the spines were harvested. The fusion sites were analyzed by gross inspection, histopathological methods, and micro-CT studies.


CONCLUSIONS
The results of this study show that an anatomically precise fusion can be accomplished by percutaneous administration of gene therapy. The next step in these studies will be extension of the technique to nonhuman primates and eventually to human clinical studies.
Laurent
Jeffrey J
JJ
Departments of Neurosurgery and Biomedical Engineering, University of Virginia Health System, Charlottesville, Virginia 22908, USA.
Webb
K Michael
KM
Beres
Elisa J
EJ
McGee
Kevin
K
Li
Jinzhong
J
van Rietbergen
Bert
B
Helm
Gregory A
GA
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D055418:Bone Morphogenetic Protein 6; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D015316:Genetic Therapy; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery*; D023421:Models, Animal; D011817:Rabbits; D013123:Spinal Fusion; D014057:Tomography, X-Ray Computed
C525816:BMP6 protein, human; D055418:Bone Morphogenetic Protein 6; D019485:Bone Morphogenetic Proteins