Percutaneous spinal fusion using bone morphogenetic protein-2 gene therapy

Tord D. Alden, Debra D. Pittman, Elisa J. Beres, Gerald R. Hankins, David F Kallmes, Benjamin M. Wisotsky, Kelvin M. Kerns, Gregory A. Helm

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

Object. 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 β-galactosidase (β-gal) gene (Ad-β-gal) was used as a control. In three groups (four rats each) 7.5 μl of virus (5 X 108 particles/μl) 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-β-gal on the left; and Group 3 received Ad-β-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.

Original languageEnglish (US)
Pages (from-to)109-114
Number of pages6
JournalJournal of Neurosurgery
Volume90
Issue number1 SUPPL.
StatePublished - Jan 1999
Externally publishedYes

Fingerprint

Bone Morphogenetic Protein 2
Spinal Fusion
Genetic Therapy
Osteogenesis
Nude Rats
Genes
Cytomegalovirus
Adenoviridae
Tomography
Galactosidases
Injections
Neurosurgery
Glycoproteins
Spine
Molecular Weight
Viruses
Bone and Bones
Proteins

Keywords

  • Adenovirus
  • Animal model
  • Gene therapy
  • Percutaneous
  • Rat
  • Spinal fusion bone morphogenetic protein

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Alden, T. D., Pittman, D. D., Beres, E. J., Hankins, G. R., Kallmes, D. F., Wisotsky, B. M., ... Helm, G. A. (1999). Percutaneous spinal fusion using bone morphogenetic protein-2 gene therapy. Journal of Neurosurgery, 90(1 SUPPL.), 109-114.

Percutaneous spinal fusion using bone morphogenetic protein-2 gene therapy. / Alden, Tord D.; Pittman, Debra D.; Beres, Elisa J.; Hankins, Gerald R.; Kallmes, David F; Wisotsky, Benjamin M.; Kerns, Kelvin M.; Helm, Gregory A.

In: Journal of Neurosurgery, Vol. 90, No. 1 SUPPL., 01.1999, p. 109-114.

Research output: Contribution to journalArticle

Alden, TD, Pittman, DD, Beres, EJ, Hankins, GR, Kallmes, DF, Wisotsky, BM, Kerns, KM & Helm, GA 1999, 'Percutaneous spinal fusion using bone morphogenetic protein-2 gene therapy', Journal of Neurosurgery, vol. 90, no. 1 SUPPL., pp. 109-114.
Alden TD, Pittman DD, Beres EJ, Hankins GR, Kallmes DF, Wisotsky BM et al. Percutaneous spinal fusion using bone morphogenetic protein-2 gene therapy. Journal of Neurosurgery. 1999 Jan;90(1 SUPPL.):109-114.
Alden, Tord D. ; Pittman, Debra D. ; Beres, Elisa J. ; Hankins, Gerald R. ; Kallmes, David F ; Wisotsky, Benjamin M. ; Kerns, Kelvin M. ; Helm, Gregory A. / Percutaneous spinal fusion using bone morphogenetic protein-2 gene therapy. In: Journal of Neurosurgery. 1999 ; Vol. 90, No. 1 SUPPL. pp. 109-114.
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