Gene Therapy May Reverse Hemophilia

A Single Treatment Allowed Patients With Hemophilia to Stop Regular Injections

From the WebMD Archives

Dec. 10, 2011 -- Sebastian Misztal recently cut himself shaving. The bleeding stopped.

Such a mundane occurrence wouldn’t usually make medical headlines. But for Misztal, a 31-year-old London businessman, and others with the inherited blood disorder hemophilia, it was a big deal. 

“It’s huge,” says Katherine Ponder, MD, a professor of medicine at Washington University in St. Louis.

In the past, Misztal has given himself regular injections to replace a protein that his body can’t make. The protein is called Factor IX (FIX). It helps blood clot.

Those injections have kept him alive. People with the severe hemophilia can bleed even if they are not injured. Spontaneous bleeding in the brain can be fatal.

But injections of clotting factors are also inconvenient and expensive. Hemophiliacs generally need the shots two to three times a week. Treatment costs run from $150,000 to $200,000 a year.

So Misztal recently became one of six men to try an experimental repair for the genetic defect that causes their condition.

Sneaking Genes Into Cells

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.”

WebMD Health News Reviewed by Laura J. Martin, MD on December 09, 2011



Ponder, K. The New England Journal of Medicine, published online Dec. 10, 2011.

Nathwani, A. The New England Journal of Medicine, published online Dec. 10, 2011.

News release, University College London.

Katherine Ponder, MD, professor of medicine, Washington University, St. Louis.

Andrew M. Davidoff, MD, chair, department of surgery, St. Jude Endowed Chair in Surgical Research, St. Jude Children’s Research Hospital, Memphis.

Amit C. Nathwani, MBChB, PhD, reader in hematology, University College London Cancer Institute, London.

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