A Very Happy Christmas for Patients with Christmas Disease

SRxA’s Word on Health couldn’t resist this story. Not only did it provide us with a seasonal healthcare title but it allowed me to blog about a condition that I have been passionate about for most of my life. As a college student, one of my friends and mentors had hemophilia. He taught me a lot about the disease, about courage and dignity and hope and despair. His death from AIDS left me saddened but determined to pursue a career in healthcare. A few years later I had the opportunity to head up a hemophilia research project in the UK. One thing led to another and I spent the next 20 years of my life involved with transfusion medicine and blood products therapies. Although I’m no longer working directly in that field, later today, I will be running a training course on hemophilia.  I guess you could say it’s in my blood!

For those of you wondering what the above recollections have to do with Christmas Disease, let me explain.

Hemophilia B, a deficiency of coagulation factor IX (FIX) is also known as Christmas disease. Hemophilia is an inherited, potentially life-threatening disorder affecting an estimated 20,000 Americans, almost all of them males. Their blood doesn’t clot properly because of a faulty gene. In severe cases, they can spontaneously start bleeding . Internal bleeding in the joints leads to debilitating movement problems and intense pain.

Unlike most diseases that were named after the doctor that discovered them, hemophilia B is rather special because it was named for the first patient described to have it. Stephen Christmas was born in London, UK in 1947.  He emigrated to Canada at a young age and was diagnosed with hemophilia at age two by Toronto’s Hospital for Sick Children. The family returned to London in December 1952 to visit relatives and, during the trip, young Stephen was admitted to hospital. A sample of his blood was sent to the Oxford Hemophilia Centre where it was discovered that he was not deficient in Factor VIII, which is normally decreased in classic hemophilia A, but a different protein, which received the name Christmas factor in his honor (and later Factor IX).

Now, almost 60 years later, scientists have described the first unequivocal evidence of successful gene therapy for hemophilia. Past gene therapy experiments improved blood-clotting for only a few weeks.

This week, the New England Journal of Medicine reports that a single intravenous injection of an adenovirus-associated virus (AAV) vector that expresses FIX  was successfully used to treat 6 patients  with hemophilia B for more than a year. This is a remarkable breakthrough, given that patients normally need to infuse FIX two or more times every week.

The six men each got a single, 20-minute infusion of AAV. Each saw the amount of clotting proteins in their blood increase from less than 1% of normal levels to at least 2%, and in one case as much as 11%.  Although that may not seem like a lot, it was enough to allow all the men to cut back on the number of regular FIX treatments, and four stopped conventional treatment altogether.

Because their prophylactic use of factor concentrate was either eliminated or reduced, dramatic cost savings were achieved. In the United States, annual costs for a single adult patient with hemophilia B are approximately $300,000. Over a lifetime this adds up to a staggering $20 million. Whereas, the AAV is estimated to cost $30,000 per patient

An editorial that accompanied the study asked: Should the practicing hematologist rush to order this gene therapy vector if it is approved by the Food and Drug Administration?

Their answer – “probably yes!”  Still, they caution that the risks of this procedure are not yet totally clear. In one patient, liver enzyme levels were found to be about five times the upper limit of normal 2 months after gene therapy.

Nevertheless this gene therapy trial for hemophilia B is truly a landmark study, since it is the first to achieve long-term expression of a blood protein at therapeutically relevant levels. If further studies determine that this approach is safe, it may not only replace the cumbersome and expensive protein therapy currently used for patients with hemophilia B, but also translate into applications for other disorders, such as alpha1-antitrypsin deficiency, and hyperlipidemias.

Now, that really would be a Christmas gift.

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