On April 1, 2016, the European Medicines Agency (EMA) approved the first ex-vivo (outside the body) gene therapy in the Western Hemisphere. Diseased stem cells are taken out of a patient’s body, corrected with a new gene using a viral vector, and then reintroduced into the patient.
With improved technologies, gene therapy is making a comeback. In a recent review published in the journal Nature Biotechnology, Laura DeFrancesco and I discovered nearly 20 gene therapy clinical trials underway for various severe conditions such as adenosine deaminase deficiency (or ADA-SCID), X-Linked SCID, chronic granulomatous disease, and Wiskott-Aldrich syndrome. We uncovered another bellwether: biotechnology and pharmaceutical companies are investing heavily in these new approaches.
Some of the earliest ex-vivo gene therapy trials were carried out in 2000 in children with ADA–SCID. The disease left children like the famed “bubble boy” David Vetter, who was treated at Texas Children’s Hospital in the 1980’s, vulnerable to deadly infections. Though 15 children in these studies were cured, five developed leukemia after the vector unexpectedly spliced near a cancer-causing gene. These results and other controversial trials led to a massive retreat from gene therapy research — until now.
What are the ethical, social, and policy implications of these new discoveries? Two caught our attention. The first is how to balance the relative risks and benefits of next-gen gene therapy trials. While these new technologies seem to be safer than the ones given 15 years ago, they are still plagued with uncertainty. Relatively few patients have received them for relatively short times, especially considering treatment is given to the very young and meant to last a lifetime. It will be important to develop laboratory tests for safety, especially for viruses that integrate genes into the DNA. We must follow these individuals over long periods of time, because the engineered cells will live as long as the patient does.
Second is an emerging debate over the cost of the treatments. Some say as a form of personalized medicine, gene therapy will add to the stratospheric costs of health care in developed countries. Others, including those developing the treatments, say as vectors and delivery methods improve, gene therapies are poised to address a global health need. These technologies, they argue, are essentially a cure, helping poor countries with large health-care burdens.
As the results from these new trials trickle in, it will be interesting to see whether the Food and Drug Administration will follow in the EMA’s footsteps, and how ethics and policy discussions in the United States will move forward from gene therapy’s early rocky start and unfulfilled promise.