Finally, some good news about gene therapy. And just in time for the holidays.

A recent study showed that giving hemophilia patients blood clotting genes can partially make up for their deficiencies and reduce bleeding. Hemophilia B is a heredity disorder caused by a defective gene for the blood clotting protein called factor IX. Researchers in Britain successfully treated six people with hemophilia by giving them a gene with a functional form of factor IX. Previous clinical trials have attempted to treat hemophilia with gene therapy, but expression of the vital factor had been short-lived. In the current study the researchers used a modified viral vector – the carrier DNA into which the factor IX DNA is inserted – that targeted the DNA specifically to the liver where factor IX is normally produced. Other studies had shown that the vector could be expressed in the livers of large animals for at least 10 years. The strategy worked, at least a year out after treatment. The participants in the study all had severe hemophilia B, meaning their bodies produced less than one percent normal factor IX levels. In a dose-dependent manner the gene raised factor IX levels in the participants between 2 and 12 percent. Not spectacular increases, but effective nonetheless. Severe hemophiliacs have to receive injections of the factor IX protein two to three times a week to avoid severe bleeding. Four of the participants were able to stop treatment injections altogether and the other two were able to extend time between injections.

Hemophilia is probably not talked about as often as many other disorders. But for people with the disease, it can be a debilitating, daily grind. Listen to Sebastian Misztal, one of the trial participants, talk about how the therapy has changed his life in the following video.

The study comes more than half a century since scientists first linked hemophilia B to a factor IX deficiency. The patient was a 10-year-old boy named Stephen Christmas. Henceforth, the disease was called “Christmas disease.” The gene therapy, however, was not without side-effects. One high-dose participant showed increased levels of transaminases, a sign of possible liver damage. Another showed a small increase in liver enzymes. The researchers treated them both with steroids.

Given that there is already a treatment for hemophilia B – factor IX concentrate injections – a fair question is: why pursue a gene therapy? One answer is cost. The cost to severe hemophiliacs who receive injections when they need them – when they’re bleeding – is about $150,000 per year. The cost for those who receive injections regularly as a prophylactic is about $300,000 per year. Over an entire lifetime the cost can exceed $20 million. The cost of the therapy is estimated at $30,000 per patient. Even if the patient has to receive multiple treatments throughout his or her lifetime it will still be the cheaper alternative by far.

One out of about every 30,000 newborn babies will have Hemophilia B. In the United States about 3,000 people have the disease. The severity of bleeding ranges widely. In the more severe cases, symptoms will be apparent early on such as when a baby is circumcised. More mild cases might not be noticed until later in life when the person experiences a trauma or undergoes surgery. It also affects men more than women as the gene for factor IX is found on the X chromosome. As with all X-linked diseases, having two X chromosomes gives women double the chance of having a normal form of the gene.

Hemophilia A, caused by a defect in clotting factor VIII, is actually much more prevalent than hemophilia B and accounts for about 80 percent of all hemophilia patients. Gene therapy scientists are starting with factor IX because it is much smaller than the factor VIII gene and more feasible to work with.

Hearing about hemophilia can conjure images of British royalty, as it is often taught in schools as the disease passed from Queen Victoria to her royal descendants all over Europe. I can still remember all those squares and circles on the science class pedigree. In 2009 scientists exhumed bones from the graves of Russian Czar Nicholas II and his family members and analyzed their DNA. The “royal disease” had been transmitted to the family from Queen Victoria. They confirmed that family members had a defective form of factor IX, or hemophilia B. Isn’t history with molecular biology fun?

But the first documentation of hemophilia goes back quite a bit further. In the Babylonian Talmud, written in the second century, Rabbi Judah commanded that “If she circumcised her first child and he died, and a second one also died, she must not circumcise her third child.”

Lucky for the third child they hadn’t yet begun to insist on an n of 3.

The current study, carried out by scientists at the University College London Cancer Institute and St. Jude Children’s Research Hospital in Memphis, Tennessee, was published in the New England Journal of Medicine. It’s a rare triumph for gene therapy, all too often delivering maladies instead of miracles. The field has proceeded much more cautiously since two French boys developed leukemia and one University of Pennsylvania teenager died after receiving gene therapy. Only six people were involved in the current study, so there’s still plenty of ground to cover before the factor IX vector can be considered a safe and effective treatment. Let’s hope the current results are not a fluke, but an indication of things to come.



video: gene therapy