Use of bone morphogenetic protein-9 gene therapy to induce spinal arthrodesis in the rodent

Gregory A. Helm, Tord D. Alden, Elisa J. Beres, Sarah B. Hudson, Subinoy Das, Jonathan A. Engh, Debra D. Pittman, Kelvin M. Kerns, David F Kallmes

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

Object. 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 7.5 x 108 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.

Original languageEnglish (US)
Pages (from-to)191-196
Number of pages6
JournalJournal of Neurosurgery
Volume92
Issue number2 SUPPL.
StatePublished - Apr 2000
Externally publishedYes

Fingerprint

Growth Differentiation Factor 2
Bone Morphogenetic Proteins
Arthrodesis
Genetic Therapy
Rodentia
Bone Morphogenetic Protein 7
Bone and Bones
Bone Morphogenetic Protein 2
Spinal Fusion
Pseudarthrosis
Radiculopathy
Tomography
Injections

Keywords

  • Adenoviral vector
  • Bone morphogenetic protein
  • Bone morphogenetic protein-9
  • Gene therapy
  • Spinal fusion

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Helm, G. A., Alden, T. D., Beres, E. J., Hudson, S. B., Das, S., Engh, J. A., ... Kallmes, D. F. (2000). Use of bone morphogenetic protein-9 gene therapy to induce spinal arthrodesis in the rodent. Journal of Neurosurgery, 92(2 SUPPL.), 191-196.

Use of bone morphogenetic protein-9 gene therapy to induce spinal arthrodesis in the rodent. / Helm, Gregory A.; Alden, Tord D.; Beres, Elisa J.; Hudson, Sarah B.; Das, Subinoy; Engh, Jonathan A.; Pittman, Debra D.; Kerns, Kelvin M.; Kallmes, David F.

In: Journal of Neurosurgery, Vol. 92, No. 2 SUPPL., 04.2000, p. 191-196.

Research output: Contribution to journalArticle

Helm, GA, Alden, TD, Beres, EJ, Hudson, SB, Das, S, Engh, JA, Pittman, DD, Kerns, KM & Kallmes, DF 2000, 'Use of bone morphogenetic protein-9 gene therapy to induce spinal arthrodesis in the rodent', Journal of Neurosurgery, vol. 92, no. 2 SUPPL., pp. 191-196.
Helm GA, Alden TD, Beres EJ, Hudson SB, Das S, Engh JA et al. Use of bone morphogenetic protein-9 gene therapy to induce spinal arthrodesis in the rodent. Journal of Neurosurgery. 2000 Apr;92(2 SUPPL.):191-196.
Helm, Gregory A. ; Alden, Tord D. ; Beres, Elisa J. ; Hudson, Sarah B. ; Das, Subinoy ; Engh, Jonathan A. ; Pittman, Debra D. ; Kerns, Kelvin M. ; Kallmes, David F. / Use of bone morphogenetic protein-9 gene therapy to induce spinal arthrodesis in the rodent. In: Journal of Neurosurgery. 2000 ; Vol. 92, No. 2 SUPPL. pp. 191-196.
@article{3d636d5368814a2985e72e2be72c3801,
title = "Use of bone morphogenetic protein-9 gene therapy to induce spinal arthrodesis in the rodent",
abstract = "Object. 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 7.5 x 108 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.",
keywords = "Adenoviral vector, Bone morphogenetic protein, Bone morphogenetic protein-9, Gene therapy, Spinal fusion",
author = "Helm, {Gregory A.} and Alden, {Tord D.} and Beres, {Elisa J.} and Hudson, {Sarah B.} and Subinoy Das and Engh, {Jonathan A.} and Pittman, {Debra D.} and Kerns, {Kelvin M.} and Kallmes, {David F}",
year = "2000",
month = "4",
language = "English (US)",
volume = "92",
pages = "191--196",
journal = "Journal of Neurosurgery",
issn = "0022-3085",
publisher = "American Association of Neurological Surgeons",
number = "2 SUPPL.",

}

TY - JOUR

T1 - Use of bone morphogenetic protein-9 gene therapy to induce spinal arthrodesis in the rodent

AU - Helm, Gregory A.

AU - Alden, Tord D.

AU - Beres, Elisa J.

AU - Hudson, Sarah B.

AU - Das, Subinoy

AU - Engh, Jonathan A.

AU - Pittman, Debra D.

AU - Kerns, Kelvin M.

AU - Kallmes, David F

PY - 2000/4

Y1 - 2000/4

N2 - Object. 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 7.5 x 108 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.

AB - Object. 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 7.5 x 108 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.

KW - Adenoviral vector

KW - Bone morphogenetic protein

KW - Bone morphogenetic protein-9

KW - Gene therapy

KW - Spinal fusion

UR - http://www.scopus.com/inward/record.url?scp=0034127731&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034127731&partnerID=8YFLogxK

M3 - Article

VL - 92

SP - 191

EP - 196

JO - Journal of Neurosurgery

JF - Journal of Neurosurgery

SN - 0022-3085

IS - 2 SUPPL.

ER -