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Fighting diseases with genetic therapy

Gene therapy has shown promise in treating blindness, cancer, hemophilia and more. Despite many challenges and setbacks, it may eventually become common.

September 13, 2012|By Elaine Herscher
(Peter and Maria Hoey, For…)

Genes make us who we are — in sickness and in health. We get our genetic makeup from our parents, of course, but in the future, we might be getting genes from our doctors too. Imagine your doctor promising to cure your cancer or heart disease by prescribing some new snippets of DNA.

For some diseases, gene therapy is already a reality. In other cases, genetic cures are still years away. Despite many challenges and setbacks — including some that are surely yet to come — experts predict that gene therapy will eventually become a crucial and even common part of healthcare.

"In the future, what you're going to see is many more diseases being approached using gene therapy," says Dr. David Russell, a hematologist and gene therapy researcher at the University of Washington in Seattle. "We'll eventually move out of the relatively rare diseases and move on to more common ones."

Research using altered genes has shown promise in treating blindness, cancer, hemophilia, heart disease, immune disorders and more. Engineered genes have already eradicated leukemia in a small group of patients; Dr. Carl June, an oncologist at the University of Pennsylvania's Perelman Medical School in Philadelphia, predicts the treatment could be widespread in as little as five years.

Virus vectors

Gene therapy is the process of adding a gene to cells to replace one that's either missing or broken. For many illnesses, researchers already know which genes should be able to do the job. The problem lies in finding the right delivery system, or vector.

These vectors are frequently benign viruses that work like Trojan horses, carrying the new genetic information to the cells. The trick is to find a vector that the patient's immune system won't destroy.

One much-studied vector is the adeno-associated virus, which tends to travel to muscle cells. This harmless virus is the workhorse behind Glybera, which is poised to become the first approved gene therapy in the Western world.

Glybera, which was approved by the European Medicines Agency in July, treats a rare genetic condition called lipoprotein lipase deficiency, or LPLD. The treatment replaces a defective gene with a healthy one and helps LPLD patients — who can't break down fat — avoid agonizing bouts of stomach pain and life-threatening pancreatitis. A single treatment is expected to last for several years. UniQure, the Dutch company that makes the drug, has yet to apply for approval in the U.S.

Virus vectors may someday seem old school. Researchers are experimenting with introducing an artificial 47th human chromosome to deliver new genes. It would exist alongside the standard 46 human chromosomes and carry additional genetic code to fight a specific disease.

Animal experiments have shown impressive progress. Gene therapies in mice have been effective to some extent in treating HIV infection, nicotine addiction, blindness and a fatal nervous system disease called spinal muscular atrophy. Transitioning these therapies to humans could take years or decades — if it ever happens at all.

Unfortunately, the history of gene therapy is riddled with disappointments. One particularly dark moment was the death in 1999 of 18-year-old Jesse Gelsinger of Tucson. Gelsinger suffered from a rare metabolic disorder called ornithine transcarbamylase deficiency, and he agreed to participate in a trial of a new gene therapy treatment. He died after his ammonia levels skyrocketed, causing brain damage followed by organ failure. An investigation found that researchers failed to report the possible risks of the drug, and the teen became the symbol of gene therapy's dangers.

Reason for hope

To many, the whole idea of gene therapy has a scary whiff of "Brave New World" about it. Skeptics question whether some promises will ever reach fruition. Even doctors who are devoting their life's work to gene therapies admit they're in it for the long haul.

"Progress in gene therapy occurs very slowly," says Dr. David Dichek, a cardiologist at the University of Washington in Seattle and a pioneer in developing gene therapy treatments for heart disease.

Still, there's plenty of room for optimism. In 2011, the story of a cancer survivor in New Jersey captivated physicians and the public.

William Ludwig, a retired corrections officer who was 65 at the time, was near death from chronic lymphocytic leukemia when he signed up to be the first patient to participate in a trial of a new gene therapy treatment.

In the trial, led by June, researchers started by removing a billion of Ludwig's T cells, immune system cells that fight tumors and infections. Then the researchers bolstered those T cells with modified genes — using a disabled version of HIV virus as the vector — and introduced the revamped cells into Ludwig's body.

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