One of the big obstacles to widespread use of gene therapy has been lack of a control mechanism that would prevent the body from overdosing. Now, an international team of researchers led by scientists at ARIAD Pharmaceuticals Inc. in Cambridge, Mass., may have come up with an answer. In the Feb. 4 issue of Science, the team reports success in regulating the production and release of insulin in diabetic mice through the use of a second, trigger drug that's taken orally. If this new method works in humans--and tests are still far off--it could mean an end to the multiple daily insulin injections that diabetics need to regulate their blood sugar.
SPIN-OFF. But development of a gene regulator could have a more important benefit: improving the overall safety of gene therapy. In September, an 18-year-old patient in a genetic-drug trial died from an overdose, and there have been hundreds of adverse reactions to gene therapies. "We need to be able to turn gene therapy off if a patient has a bad reaction to it," says Helen M. Blau, director of Stanford University's gene therapy program.
In the experiments described in Science, researchers were able to trigger and control release of insulin in mice with a companion drug. After being injected with a modified version of the gene that produces insulin, the mice began producing insulin in their leg muscles. But the amount of insulin released by the mice's muscles depended on the dose of the drug: The larger the dose, the more insulin. Without the drug, which could be given in pill form for humans, virtually no insulin was released.
This technology could lead to therapies that would replace other injectable medicines--leptin for obesity or endorphins for pain. And the best part? Because it's an adaptation of a natural cellular process, ARIAD researchers believe there will be few side effects.