Gene Therapy Progress is Summarized

Scientific American reports that gene therapy is starting to live up to its early promise. In the past six years the experimental procedure for placing healthy genes wherever they are needed in the body has restored sight in about 40 people with a hereditary form of blindness. Doctors have seen unprecedented results among another 120-plus patients with various cancers of the blood—several of whom remain free of malignancy three years after treatment. Researchers have also used gene therapy to enable a few men with hemophilia, a sometimes fatal bleeding disorder, to go longer without dangerous incidents or the need for high doses of clotting drugs.

Although gene therapy is still not available in hospitals and clinics, that is likely to change in the next decade. Europe approved its first gene treatment, for a rare but extremely painful disorder called familial lipoprotein lipase deficiency, in 2012. At the end of 2013 the National Institutes of Health removed some of the regulatory speed bumps that the agency now considers unnecessary. The first U.S. approval of a commercial gene treatment, some industry watchers predict, may come in 2016. Gene therapy, after its lost decade, is at last beginning to fulfill its destiny as a revolutionary medical treatment.

Even adenovirus, which caused Gelsinger’s death, is still in clinical trails as a gene therapy vector. Investigators restrict its use to parts of the body where it is unlikely to cause an immune response. One promising application is to treat “dry mouth” in patients undergoing radiation for head and neck cancer, which damages the salivary glands, located just under the surface of the inside of the cheek.

The nih is running a small clinical trial that involves inserting a gene that creates channels for water into the glands. Because the glands are small and contained, and the experimental design calls for 1,000-fold fewer viruses than were used on Gelsinger, the chances of an immune overreaction are reduced. In addition, viruses that do not hit their target cells should wind up in a patient’s drool, either swallowed or spit out, with little chance of irking the immune system. Since 2006, six of 11 treated patients have been shown to produce significantly more saliva. Bruce Baum, a dentist and biochemist who led the research before he retired, calls the results “cautiously encouraging.”

Emboldened by these successes, medical researchers have moved beyond treating hereditary diseases to trying to reverse genetic damage that naturally occurs over the course of a lifetime.

With safer viral delivery systems in hand, gene therapy specialists are now tackling the greatest challenge that any new drug faces: earning the approval of the U.S. Food and Drug Administration. This daunting step requires so-called phase III clinical trials, which are designed to assess efficacy in a larger group of volunteer patients and typically take one to five years to complete (the time varies widely). As of the end of 2013, about 5 percent of approximately 2,000 clinical trials for gene therapy had reached phase III. One of the furthest along is aimed at Leber congenital amaurosis—the condition that was robbing Haas of his sight. So far several dozen patients have had corrective genes inserted into both eyes and are now able to see the world.

China was the first country to approve a gene treatment, in 2004, for head and neck cancer. In 2012 Europe approved a gene therapy–based drug called Glybera to treat familial lipoprotein lipase deficiency. Working copies of the mutant gene wrapped in AAV are injected into the leg muscles. Netherlands-based company UniQure is in early talks with the fda about approval in the U.S. One potential stumbling block: the price tag for a single curative dose is $1.6 million, but that cost may come down as researchers develop more efficient procedures.

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