After a single gene-therapy treatment, four of the men started making enough of their own clotting factor that they no longer needed the regular protein injections that are currently used to prevent bleeding episodes. The other two required the protein injections but much less frequently than before, according to the paper, which was published online Saturday in the New England Journal of Medicine.
"The idea of treating hemophilia with gene therapy has been around for 25 years, but the problem was how to do it right," says Ronald G. Crystal, chairman of the department of genetic medicine at Weill Cornell Medical College, who is working on gene-therapy research but was not involved in the trial. "This is an important breakthrough because it is the first success in one of the plasma deficiency disorders and shows gene therapy is feasible."
Hemophilia B is caused by a defect in the gene that makes a protein called Factor IX, which is crucial for normal blood clotting. About 1 in 30,000 individuals, usually men, inherit the mutation. Without enough clotting factor, patients can have frequent, painful bleeding episodes.
With gene therapy, scientists try to correct the problem by delivering a normal gene to the body, using what is known as a vector to insert the gene into cells -- usually a virus that is genetically altered to contain human DNA.
Researchers altered the DNA of a common virus so that it would include the instructions for making FIX.
They then injected the men with the altered virus. They hoped that it would do what all viruses do: infect cells and hijack their operating instructions.
Ordinarily when viruses infect cells, they turn the cells into factories that crank out more copies of the virus. That keeps the infection going.
In this case, the infected cells churned out the missing protein.
After a single treatment, four of the six men in the study have been able to stop their weekly protein injections altogether. Two others have been able to stretch the time between their shots from days to up to two weeks.
"You've got people who are maybe not quite cured," says Ponder, an expert on blood disorders who was not involved in the research.
The study and an editorial by Ponder are published in The New England Journal of Medicine.
The results are also scheduled to be presented at the annual meeting of the American Society of Hematology in San Diego.
Hope on the Horizon for Hemophilia and Other Diseases
So far, researchers have only been able to coax the body to make the protein that helps people with the less common form of the disease, hemophilia B.
But researchers say this approach could work for people who have the more common form, hemophilia A, too. They just need to find the right virus to deliver the genes that would help that disease.
"I think this approach will lead to a cure. I think it's not there yet," says study researcher Andrew M. Davidoff, MD, a pediatric surgeon at St. Jude Children's Research Hospital in Memphis, Tenn.
"We have made a significant impact on the severity of the disease," Davidoff tells WebMD. "We are looking to cure patients, and I think with improvements in the vector and higher doses, we will be able to cure them."
Before they were enrolled in the study, the six men all had levels of FIX protein that were less than 1%. After the gene therapy, their FIX levels improved to 2% to 11%.
That's high enough to prevent spontaneous bleeding events. But it's not enough clotting factor to keep them out of danger during surgery, for example, or in the event of other significant trauma.
Researchers think they may be able to give people with hemophilia B higher doses of the altered virus to help boost FIX levels even more.
Questions Remain
But it's unclear how much people will be able to tolerate.
In this study, patients who got the highest doses made the most FIX. But they also saw their liver enzymes spike, a sign of inflammation.
"We were able to control this inflammation with a very short course of steroids," says study researcher Amit C. Nathwani, MBChB, PhD, a hematologist at University College London.
After steroid treatment, liver enzymes returned to normal. And patients continued to make FIX protein on their own, though their levels dropped slightly.
It's also not clear how long the treatments may last.
All patients who got the gene therapy continue to make FIX protein. Some have been followed for nearly two years.
But as liver cells die, the treatment could wear off. In animal studies, results of gene therapies that target liver cells have lasted for 10 years or more.
Even if it's temporary, the gene therapy is likely to save money. If it is approved by the FDA, the treatment is estimated to cost around $30,000 per patient.
It may also turn out to be safer than injecting blood products. In the 1980s, many hemophiliacs were infected with HIV after being treated with clotting factors that contained the virus.
Nathwani says many people with hemophilia in developing countries continue to face that risk, if they are able to get treatment at all.
"Eighty percent of hemophilia patients around the world have no access to treatment," he says. "This is one of the reasons why we wanted to develop a simple gene transfer approach," which could be delivered in almost any clinical setting, he says. "This is life changing."
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