Winning paper shows that gene therapy may have a role in managing degenerative disc disease


The 2011 winning paper of The Spine Journal’s Outstanding Paper Award for basic science has found that gene therapy may have a role in managing degenerative disc disease.

Lead author Steven Leckie, Department of Orthopaedic Surgery, University of Pittsburgh, Pennsylvania, USA, and his co-investigators reviewed the use of AVV2-BMP2 and AVV2-TIMP1 to manage degenerative disc disease in New Zealand white rabbits. Explaining the purpose of the study, he said: “BMP2 is known to induce proteoglycan production in the intervertebral disc and TIMP1 is anti-anabolic in that it prevents the breakdown of proteoglycan. The problem with growth factors is that they are transient, so the philosophy of gene therapy is that we might be able to induce a sustained response from the host.” He added that, in their study, they used the adeno-associated virus as their vector because it has been shown to be safer than other vectors used in previous studies.


In the study, six rabbits were used as controls (therefore, did not undergo any procedure), four underwent a sham procedure (undergoing a surgical exposure but did not receive degeneration surgery), eight were surgically exposed and punctured with a 16-gauge needle (reliably shown to induce degeneration), eight underwent the puncture procedure and were treated with AVV2-BMP2 gene therapy, and eight underwent the puncture procedure and were treated with AVV2-TIMP1 gene therapy. Leckie said: “The outcomes that we measured included MRI, histology, biomechanics, and biochemistry.”


Both the control rabbits and those that underwent the sham procedure did not show signs of disc degeneration after 12 weeks, but the rabbits in the puncture group and the treatment groups did. About the treatment groups, Leckie said: “Although they did have some degree of disc degeneration, they appeared to have less degeneration than the puncture group.” He added: “We also collected serum biomarkers for C-telopeptide II, which is the breakdown product of C-terminus of collagen II and can be measured in the serum. At 12 weeks, the control rabbits had a slight increase, the puncture rabbits had significantly higher serum values, and the treatment groups had values that fell well below those of the puncture group.”


Histological data were also collected. Leckie said: “The discs of the control and sham rabbits appeared to be normal. The puncture discs appeared relatively acellular and more fibrotic, and the discs that were treated with AVV2-BMP2 or AVV2-TIMP1 gene therapy had a relative maintenance of cellularity and relative preservation of their architecture.”


Leckie concluded by saying: “We have MRI evidence, serum biomarker evidence, biomechanics evidence, and histology evidence that gene therapy treatment with AVV2-BMP2 or AVV2-TIMP1 might help slow the course of disc degeneration in a rabbit model.”