Is Gene-Therapy Medical Treatment Ready for Prime Time?

Is Gene-Therapy Medical Treatment Ready for Prime Time?

At first it sounded like science fiction, curing genetic diseases by giving people new genes. Then it seemed like simple fiction: while theoretically possible, gene therapy appeared unlikely to become a true therapeutic option, the field having suffered years of complications and high-profile setbacks. But over the past year, a series of small but intriguing advances has suggested that the technique may hold real future potential.

In September, researchers at the University of Washington reported in the journal Nature that they had produced color vision in squirrel monkeys, which are normally born colorblind. Using a tiny syringe, researchers injected the single missing gene for color vision into the monkeys’ eyes. The result was clear: monkeys that previously could not distinguish red, green and gray were easily able to pass a simian equivalent of a color-detection test.

Another study published in the Lancet in October found that gene therapy had restored partial vision to five children and seven adults with a congenital eye disease that causes blindness. And a paper published earlier this month in Science reported the successful treatment of two children with ALD, or adrenoleukodystrophy — a neurological disorder that leads to progressive brain damage and death in two to five years.

In the most recent study, published in November, researchers at Nationwide Children’s Hospital in Columbus, Ohio, reported they had successfully gotten monkeys to grow bigger, stronger muscles within weeks — no anabolic steroids, exercise or genetic engineering required. Scientists injected genes directly into the right quadriceps of six healthy monkeys, and eight weeks later, the changes were plainly visible. The muscles in each monkey’s right leg were larger and measurably more forceful than those in the left leg, and the effects remained for 15 months.

That study built on previous research by the Columbus-based team, which had successfully used gene therapy to treat rodents with the muscle-wasting disease muscular dystrophy. “We wanted to raise the bar and test a species closely related to humans,” says neuroscientist Brian Kaspar, a co-leader of the study published in Science Translational Medicine.

The single gene injected into the monkeys was coded for the naturally occurring protein follistatin, which blocks the function of another protein called myostatin that hinders muscle growth. Past research in mice that were genetically engineered to have an extra copy of the follistatin-producing gene has shown that blocking myostatin, by increasing follistatin, causes muscles to bulk up fast. What Kaspar and his team found was that the same effect could be achieved simply by injecting genes — ferried aboard a small, non-disease-causing virus known as AAV, or adeno-associated virus — into the muscle. They further discovered that once the gene was delivered into the muscle-cell nucleus, muscles began producing their own constant supply of follistatin, and muscle fibers kept growing. Think of it as the body producing its own muscle-boosting drugs.

The findings got headlines, not least because they immediately raised the possibility of power-hungry athletes someday using gene doping to improve performance — a technique that would be much harder to detect than using performance-enhancing drugs. And while myostatin-blocking drugs are not yet available, the pharmaceutical companies Amgen and Wyeth are currently experimenting with myostatin inhibitors, with encouraging early results, and it’s clearly something that antidoping agencies around the world are concerned about. The World Anti-Doping Agency has banned gene doping, and included “agents modifying myostatin function” on its list of prohibited substances.

Scientists do not yet know whether myostatin-related gene therapy will even work in humans. Given the financial and regulatory hurdles to launching a first-phase trial, it could take years and several million dollars before researchers could replicate their animal findings in people. But advances like the muscle trial in monkeys help attract funds — largely from advocacy groups like the Muscular Dystrophy Association and charitable organizations founded by patient families, as well as drug companies and the federal government — to a field that has until now been somewhat better known for its failures. In 2003, for instance, two French children with a rare genetic immune disorder developed leukemia after they received gene-therapy injections containing retroviruses. The other 18 children in the trial were cured, but the setback reverberated through the field, dissuading researchers and funding. “A lot of financial interest has disappeared since it became clear that it’s going to take a long time and it’s not going to be easy [to develop gene-therapy drugs],” says Hank Greely of Stanford University’s Center for Biomedical Ethics.

But despite gene therapy’s public-image problem, scientists are optimistic. Many believe that over the next four to five years, they will be able to apply what they have learned from studying gene therapies for rare diseases to the treatment of more common ailments like epilepsy, arthritis and congestive heart failure. “[Gene therapy] still needs one killer app. One clear, unambiguous success,” says Greely. “And then the money will flood in.”

Read “A Gene to Cure Blindness.”

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