1. ¹Center for Molecular Orthopaedics, Harvard Medical School, Boston, Massachusetts, USA
2. ²Gene Therapy Laboratory, Department of Orthopaedics and Rehabilitation, University of Florida College of Medicine, Gainesville, Florida, USA
3. ³Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA

Correspondence: Christopher H. Evans, Center for Molecular Orthopaedics, Beth Israel Deaconess Medical Center, RN-115, 330, Brookline Avenue, Boston, Massachusetts 02215, USA. E-mail: cevans@bidmc.harvard.edu

Received 21 August 2008; Accepted 26 October 2008; Published online 9 December 2008.

Abstract

Orthopedic disorders, although rarely fatal, are the leading cause of morbidity and impose a huge socioeconomic burden. Their prevalence will increase dramatically as populations age and gain weight. Many orthopedic conditions are difficult to treat by conventional means; however, they are good candidates for gene therapy. Clinical trials have already been initiated for arthritis and the aseptic loosening of prosthetic joints, and the development of bone-healing applications is at an advanced, preclinical stage. Other potential uses include the treatment of Mendelian diseases and orthopedic tumors, as well as the repair and regeneration of cartilage, ligaments, and tendons. Many of these goals should be achievable with existing technologies. The main barriers to clinical application are funding and regulatory issues, which in turn reflect major safety concerns and the opinion, in some quarters, that gene therapy should not be applied to nonlethal, nongenetic diseases. For some indications, advances in nongenetic treatments have also diminished enthusiasm. Nevertheless, the preclinical and early clinical data are impressive and provide considerable optimism that gene therapy will provide straightforward, effective solutions to the clinical management of several common debilitating disorders that are otherwise difficult and expensive to treat.