GENE THERAPY IN ORTHOPEDICS

Abstract

Gene therapy may be defined as the introduction of a form of nucleic acid into the cells of a patient for the amelioration of a disease process. There are three basic approaches to the this lofty goal of disease amelioration: (I) replacement of defective genes; (2) augmentation of normal gene function (or interference with proliferative controls); and (3) blocking of disease triggering genes {oncogenes) at the RNA or DNA levels.( I)

Human gene therapy currently is limited to manipulations affecting somatic, differentiated cells. The risk of inadvertent transfer into reproductive cells is low and difficult to quantitate. Such concerns can be minimized and should not act as an absolute contraindication for proceeding with Phase I trials for diseases that cause serious disability. Germ line gene therapy where reproductive cells are being manipulated is unlikely to become accepted in the foreseeable future. This is because the potential risk and unpredictable results may be transferred to the patient's descendents. Specific legal restrictions have been developed in Europe to prevent attempts at germ line therapy. (2)

Somatic cell therapy can be seen as a special form of organ transplantation with a specific transfer of information without surgical intervention. Somatic gene therapy has a limited duration of effect and will have to be repeated on a regular basis because the somatic cells of the body constantly are being replaced. Four thousand monogenetic deficiencies are candidates for somatic gene therapy. Additionally targeted elimination of cancer cells, treatment of AIDS, vascular disorders, rheumatoid disorders and cell marking have been the basis of clinical trials using gene thcrapy.(2)