Gene therapy and cement injection for restabilization of loosened hip prostheses.

Loosening of orthopedic hip prostheses is an increasing health problem. In elderly patients with comorbidity,revision surgery may lead to high mortality rates. A less invasive surgical technique is therefore required to reduce these patient risks. To this end a percutaneous gene therapy approach was designed to destroy the periprosthetic loosening membrane, and enable refixing of the hip prosthesis with percutaneous bone cement injections under radiological guidance. In this phase 1/2 dose-escalating gene therapy clinical trial, 12 patients were treated. Toxicity and hip function variables were monitored up to 6 months posttreatment. All patients completed the study and no dose-limiting toxicity was observed. Improvement in walking distance, independence,and pain was demonstrated particularly in patients receiving 3 x 10(10) and 1 x 10(11) viral particles. Taken together, these data show that this gene therapy approach targeted at the interface membrane around a loosened hip prosthesis is a feasible treatment option for elderly patients for whom surgical intervention is not appropriate.