Spine fusion by gene therapy.
Over 250 000 patients each year undergo a spine fusion procedure in the US. This constitutes 50% of all bone graft procedures. Despite best efforts, a large percentage of spine fusions (up to 35%) fail to form a solid bony arthrodesis. This is a significant clinical problem and has led to research in bone formation biology to augment spine fusion rates. Both recombinant and purified osteoinductive cytokines have been studied in pilot and pivotal studies in humans. At this point, recombinant human bone morphogenetic protein-2 has received FDA approved for lumbar interbody application with titanium cages. Despite these successes, limitations of directly applying osteoinductive proteins related to cost and carriers remain to be overcome. Gene therapy for spine fusion and other bone healing applications are being pursued as an alternative strategy. This article will review the state of the art of local gene therapy for bone formation and to highlight specific issues, which must be addressed when pursuing such a program. A critical step in using gene therapy for bone formation is choosing an appropriate osteoinductive gene. In choosing the gene, one must consider the differences in efficacy of the gene as well as the gene availability due to proprietary constraints. The choice of delivery vector is important. Factors such as the potency of the gene and the specific application intended play a role in this decision. Next, the effective dose, transduction time, and gene transfer method must be established. The choice of carrier material to form the scaffold for the new bone formation is another critical step that must be optimized for successful bone formation. Finally, a strategy for in vitro and in vivo testing must be developed to maximize the chances of success in human trials.
Yoon
S T
ST
Department of Orthopaedic Surgery, The Emory Spine Center, Atlanta, GA 30033, USA.
Boden
S D
SD
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology; D003598:Cytoskeletal Proteins; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D010012:Osteogenesis; D013123:Spinal Fusion / Q000379:methods*
D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; C484380:PDLIM7 protein, human