Gene Therapy: Medicine for Your Genes

PRODUCERS: John Rudolph

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New & Noteworthy, 2007
by Jennifer Jongsma

In Gene Therapy: Medicine for Your Genes, The DNA Files looked at a visionary but challenging technology: gene therapy. The first gene transfer trials were approved in 1989, but the field has yet to live up to its early hope and hype. The basic concept of gene therapy remains seemingly simple: introduce into a target cell a piece of genetic material that will either cure the disease or slow down its progression. Unfortunately, researchers still struggle to safely deliver genes to the right place. Patients' immune systems often see viral vectors as exactly what they are, viruses, and attack accordingly. Furthermore, scientists warn that certain forms of gene therapy may cause patients to develop cancer when the inserted genes disrupt the normal process of healthy cells.

Researchers have attempted a variety of gene delivery methods, such as fat capsules, synthetic vectors, nose drops, and aerosol delivery. So far, disarmed viruses remain the most efficient method. Viruses, however, also have increased potential to induce dangerous unwanted effects. The field of gene therapy has taken several blows in recent years, including the 1999 gene therapy-related death of Jesse Gelsinger and the 2002 gene therapy-induced leukemia of a 3-year-old boy with X-linked severe combined immunodeficiency syndrome ("Boy in the Bubble" syndrome). Jolee Mohr, a 36-year-old woman with rheumatoid arthritis, died in July 2007 after receiving an investigational gene therapy product in a clinical trial. A gene intended to reduce inflammation and disease was delivered into the affected joint using a vector derived from an adeno-associated virus (AAV). Four days after the experimental treatment was injected into Mohr's right knee, a sudden infection raged through her body and caused her organs to fail. The U.S. Food and Drug Administration immediately put the trial on hold pending investigation into the cause of Mohr's death. Targeted Genetics, the Seattle, Wash., company conducting the study, issued a statement saying that Mohr's clinical course did not appear to be a consequence of exposure to the AAV vector. Postmortem tests revealed that Mohr died from a massive fungal infection, rather than directly by the genetically altered viruses she was given. The National Institutes of Health Recombinant DNA Advisory Committee, which is working with the FDA on the scientific and safety implications of gene therapy, said further tests are needed to see if the treatment itself somehow contributed to Mohr's death, perhaps by leaving her vulnerable to infection.

Researchers also can point to a few successes. In 2005, clinicians at Washington University School of Medicine in St. Louis restored newborn mice and dogs with hemophilia A to normal health. They had successfully introduced the gene for a missing protein, clotting factor VIII, into the animals' cells. The next step is to test gene therapy in primates with hemophilia, moving closer to testing in humans. In 2007, a team led by researchers at New York-Presbyterian Hospital/Weill Cornell Medical Center completed an early stage clinical trial in 11 men and 1 woman with Parkinson's disease. Their viral vector carried a gene that instructs the cell to make GABA, a neurotransmitter that helps quiet excessive neuronal firing. Patients with Parkinson's disease, besides losing many dopamine-producing brain cells, develop substantial reductions in the activity and amount of GABA in their brains. The study proved safe and resulted in improved motor function over the course of one year. These small advances provide hope to many patients with limited options.

Original Program Description, 1998

Imagine a cure for cancer in an injection. Imagine medicine that changes the genetic code inside your body. Imagine a treatment that can conquer our most serious diseases - a medicine delivered to our cells by a virus much like the one that causes the common cold, or even AIDS.

Gene therapy holds the prospect of great hope as well as the danger of the unknown, as researchers, scholars, doctors, and patients weigh the benefits and the risks of a medical treatment that's still in its infancy.

The goal of gene therapy is to cure disease by treating it on the genetic level. The possibility of success in this effort has spawned a great deal of speculation and an equal amount of controversy. It has also generated a lot of research fueled by millions of dollars in public and private funds.

Gene therapy is not a medical miracle — at least not yet. Still, some people with deadly diseases are willing to take the huge risk of trying an experimental medicine. In this show, we follow the case of one of them: Don Hardy, a 66-year-old former construction worker who has mesothelioma, a form of incurable lung cancer. Hardy is the first to receive a highly experimental form of gene therapy treatment. Choosing to reject conventional treatment in favor of gene therapy, he becomes a "human guinea pig." The DNA Files accompanies Hardy throughout his ordeal, as his doctor tells him the results of his latest x-rays and as he contemplates his fate both with and without gene therapy.

Though around 3,000 people have been treated with gene therapy, no one has ever been cured. If gene therapy does produce a cure someday, it's sure to be big business. What impact will it have on health care and health insurance? Who will be able to afford it? Explore the ethics and attitudes behind potential treatments that could one day be part of an enormous biotech marketplace.

Then, imagine the future for yourself.