Gene Therapy a Boon for 6 Hemophilia Patients

SATURDAY Dec. 10, 2011 -- A single treatment of gene therapy dramatically improved symptoms and quality of life in a small group of men with hemophilia B, an uncommon form of the bleeding disorder, a new study suggests.

"It is a small trial in that only six patients have been treated thus far, but it has been rather successful and I think it will encourage further use of this approach in the very near future, both by us and others," said senior author Dr. Andrew Davidoff, chairman of the department of surgery at St. Jude Children's Research Hospital in Memphis. "At this point, we're a little shy of being able to call it a cure, but it's a good start."

Six severely affected patients were infused with a correct version of the gene that makes a protein called factor IX, which is essential for blood clotting. Following treatment, four were able to stop receiving protein injections to prevent bleeding episodes and so far they have not suffered spontaneous bleeding. The two other patients have increased the time period between factor IX injections previously required at least twice a week. The patients ranged in age from 27 to 64.

The study, scheduled for presentation Saturday at the annual meeting of the American Society of Hematology in San Diego, was published concurrently in the New England Journal of Medicine.

Carried on the X chromosome -- making it almost exclusively a disease of men -- the hemophilia gene variant prevents blood from clotting normally. About 1 in 25,000 males inherit the gene mutation for hemophilia B, which is also known as Christmas disease in honor of Stephen Christmas, the first person diagnosed with the disorder in 1952. Hemophilia B is far less common than the better-known hemophilia A, which affects about 1 in 5,000 males born in the United States.

Both forms of the blood disorder, which often led to early death before treatments were developed, can cause disabling, painful bleeding episodes and spontaneous bleeding.

During the study, the correct gene was delivered to patients' livers using a so-called "vector," a virus that doesn't cause disease in humans. Two patients each received a low-, medium- or high-dose of the vector. Following treatment, factor IX levels rose in all six patients from less than 1 percent of normal levels to between 2 and 12 percent, increasing the most in the two patients who received the highest dose.

Even at these below-normal protein levels, the treatment made a marked difference in patients' quality of life, said Dr. Louis Aledort, a professor of medicine at Mount Sinai School of Medicine in New York City.

"You automatically change the disease from severe to mild that almost never causes trouble, and they won't bleed [abnormally] except for situations such as surgery," he said. "This is exciting because it's happening in people and it has gone beyond an animal model."

If gene therapy can someday be extended to many others with hemophilia B, it could save a great deal of money, according to Dr. Katherine Ponder of Washington University School of Medicine in St. Louis, author of an accompanying journal editorial. While the vector costs about $30,000, the annual cost of maintenance treatments for a single hemophiliac can range from $150,000 to $300,000, she said.

But developing a similar gene therapy for the more-common hemophilia A is problematic, Davidoff said, because the missing protein in that form of the disorder is much larger and therefore more difficult for a vector to deliver to the liver. Hemophilia A is also more likely to generate an immune response from the body that may be hard to control, he said.

Two of the gene therapy patients with hemophilia B suffered mild immune responses that required steroid treatment, the study said. But the first patient who received the gene has maintained steady levels of the factor IX protein for more than 18 months, Davidoff said.

"We don't know for sure that the gene will stay there . . . time will tell," he said. "Thus far, the approach has worked very well in terms of safety, but it needs to be studied more carefully and in greater numbers."

More information

The U.S. National Library of Medicine has more about hemophilia B.

Posted: December 2011


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