Disease could be first triumph for gene therapy

WEDNESDAY, June 9 (HealthScout) -- The blood disease that felled royal families and thinned the ranks of Europe's aristocracies may be cured by the most modern efforts of modern medicine.

Hemophilia, a deadly disorder that prevents blood from clotting and can cause patients literally to bleed to death from a slight flesh wound, may soon succumb to gene therapy, say researchers who have developed a way to correct the problem in mice.

Dr. Christopher Walsh and colleagues at the University of North Carolina at Chapel Hill (UNC) say they successfully treated hemophiliac mice using viral genes carrying instructions to make a protein that helps blood clot. The work, which is being presented today to the American Society of Gene Therapy meeting in Washington, D.C., could mark the first cure credited to the gene therapy.

More than 15,000 people in the United States suffer from hemophilia, a genetic disorder in which the body fails to make enough of the clotting factors that prevent excess bleeding. Most have hemophilia A, in which levels of clotting factor VIII can be less than 1 percent of normal.

The disease can be treated with regular injections of these proteins, but the shots are expensive -- about $4,000 a dose -- and last only half a day. In addition, the transfusions hold a small risk of infection from viruses like hepatitis C and HIV.

The elusive goal of hemophilia researchers has long been a one-shot treatment to reverse the condition. Lately a number of scientists have converged on gene therapy techniques.

Hemophilia, it turns out, is well-suited for such an approach because, unlike most other diseases, it requires only minimal success to be effective. Not only is it caused by a mutation in a single gene, but, experts say, blood can clot well with only about 5 percent of its normal level of the thickening protein.

Walsh and his group knitted the gene for human clotting factor VIII to the DNA of the adeno-associated virus, or AAV. They then injected the package into mice engineered to have hemophilia.

As the harmless microbe infected the animals, some of their cells began expressing the DNA rider, churning out clotting factor VIII. Blood levels of the protein rose up to 20 percent of normal. Nearly a year later, the mice continue to make clotting factor VIII, a sign the treatment has securely taken hold, Walsh says.

Next Walsh's group plans to test the technique in dogs and then in humans. "In patients who have nothing, if you can get them up to 5 percent [of normal] that would have a major impact on their disease," says Walsh. That level also would ease joint disease, chronic arthritis and deformities common in hemophiliacs. "If you could get them up to 20 percent, you might think of this as a curative. This disease may be the first one that is cured by gene therapy," Walsh says.

The AAV method also is being explored to treat many other conditions, including Parkinson's and Huntington's diseases.

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Despite the optimism, success in mice doesn't always lead to success in people. The new treatment is a long way from being ready for patients, although Walsh says human trials will begin sometime in the "near future