Gene Therapy Researchers React to Field's Pitfalls and Promises
Woo, Savio L. C., FDA Consumer
THE LAST WORD
The possibility of correcting human genetic disorders by gene therapy caught the imagination of the scientific community as well as that of the public long before the first clinical gene transfer experiment was launched ten years ago. During the ensuing decade, however, the extraordinarily high level of expectation has proven to be grossly optimistic. This prompted Dr. Harold Varmus, then Director of the National Institutes of Health, to appoint two separate committees in the mid-1990s to evaluate the field of gene therapy. The committees independently concluded that clinical applications of gene transfer could not possibly succeed without adequate scientific and technological support, as well as sufficient preclinical studies in relevant animal models of human disease to validate treatment efficacy.
The scientific community has taken these constructive criticisms to heart during the past few years, and dramatic progress has been made in the basic science of viral and non-viral vector development used to transfer genes into patients. As a result, some approaches appear to be working. The Hemophilia B trial currently being conducted at the Children's Hospital of Philadelphia and Stanford University employs intramuscular `delivery of the gene expressing human Factor IX, a protein involved in blood clotting. Patients in this trial have exhibited much improved whole blood clotting times for months after the gene treatment. Children in Paris with X-linked SCID, an inherited disorder that destroys the immune system, are able to live at home normally after genetic treatment of bone marrow stem cells. While both trials are in early phases, the encouraging results do provide proof of the scientific principle that human genetic disorders can be corrected by gene transfer.
In September 1999, clinical experiments in gene transfer research suffered their first patient loss as a direct consequence of the gene treatment itself. The patient was a 19-year-old male with a metabolic disorder who received a high dose of a genetic treatment directly into his liver at the University of Pennsylvania. He died from multi-organ failure induced by an adult respiratory distress syndrome secondary to a systemic inflammatory response to the method used to deliver the new gene.
Initial public response to the tragic incident was rather mild, as it is understood that medical research is not without risks. But public perception of clinical gene therapy took a precipitous turn for the worse after the FDA cited the University of Pennsylvania investigators in December 1999 for multiple protocol violations in the trial. …