Gene Treatment for Hemophilia Shows Promise

The idea of replacing faulty genes with functional ones is alluring, but it's come under severe criticism since a volunteer patient with an inherited enzyme deficiency died last fall (Science, 17 December 1999, p. 2244). Now an early report from a different research team suggests that, at least for hemophilia, there's reason for guarded optimism about a new gene therapy.

People with hemophilia have inherited a genetic defect that limits the production of blood-clotting factors. That puts them at risk of dying from trauma or internal bleeding. Regular and expensive transfusions currently allow most hemophiliacs to keep their disease in check. The goal of this treatment is to maintain a clotting factor level that is 1% or more of the level in normal blood.

In hopes of finding a better treatment for hemophilia, hematologist Katherine High of the Children's Hospital of Philadelphia and colleagues started working on a gene therapy strategy 6 years ago. After success with mice and dogs, they began a preliminary clinical trial with three patients. The team injected the volunteers in the thigh with a virus that had been engineered to carry a gene that codes for a clotting factor. The virus infected nearby muscle tissue, where cells stepped up their production of clotting factor, the team reports in the March Nature Genetics.

Although this preliminary test--intended to test for safety, not efficacy--used very low doses of the virus, the patients responded well. One person needed 50% less clotting factor during the first 100 days after the injection, and another needed 80% less. The third patient didn't show a clear response. The researchers found no side effects.

High is "cautiously optimistic" that the therapy might provide a new way to treat hemophilia, perhaps by converting severe forms of the illness into a milder and more manageable condition. Although the early results are "far from a clear-cut case of successful gene therapy," says molecular biologist Kotoku Kurachi of the University of Michigan, Ann Arbor, he says that the treatment could prove very useful--if higher doses are safe and treated tissue continues to produce clotting factor over the long term.