Use of bone morphogenetic protein-9 gene therapy to induce spinal arthrodesis in the rodent.
OBJECTIVE
Bone morphogenetic proteins (BMPs) have been shown to have significant osteoinductive activity in numerous in vitro and in vivo assay systems, and BMP-2 and BMP-7 are currently being evaluated in human clinical studies. 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 direct or ex vivo gene therapy techniques is also currently being evaluated and has shown promise in several mammalian models. The present study was designed to evaluate the efficacy of the use of direct, percutaneous BMP-9 adenoviral gene therapy to promote spinal fusion in the rodent.


METHODS
Each animal was injected with 7.5x10(8) pfu of a BMP-9 adenoviral vector in the lumbar paraspinal musculature and allowed to survive 16 weeks. Computerized tomography studies and histological analysis demonstrated massive bone induction at the injection sites, clearly leading to solid spinal 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.
Helm
G A
GA
Department of Neurosurgery, University of Virginia Medical Center, Charlottesville, USA. gah9r@virginia.edu
Alden
T D
TD
Beres
E J
EJ
Hudson
S B
SB
Das
S
S
Engh
J A
JA
Pittman
D D
DD
Kerns
K M
KM
Kallmes
D F
DF
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D001861:Bone Regeneration / Q000235:genetics*; D015316:Genetic Therapy; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008159:Lumbar Vertebrae / Q000473:pathology; D008297:Male; D051381:Rats; D011923:Rats, Nude; D013123:Spinal Fusion; D014057:Tomography, X-Ray Computed
D019485:Bone Morphogenetic Proteins