Gene therapy for Hemophilia B

For the millionth time-- Viruses are not just pathogens that make us sick. In the modern world, viruses have been domesticated, and are now used to treat/cure diseases. Example #gazillion: Hemophilia B:

Adenovirus-Associated Virus Vector-Mediated Gene Transfer in Hemophilia B

This study is far from perfect, and of course very preliminary, but still very exciting. Hemophilia B is a disease in males caused by point mutations/deletions/etc in the clotting Factor IX gene. If you dont make Factor IX, you wont clot properly, and will have all of the health issues we associate with hemophilia.

The good news is, is that today Hemophilia B is readily treatable with pharmaceutical Factor IX.

The bad news is, patients have to get infusions of Factor IX all the time. Like, several times a week.

The scientists in this paper took six Hemophilia B patients, and treated them with an Adeno-Associated Virus-8 (two at low, medium, and high doses of virus) that contained a functional copy of the Factor IX gene.

Four of them of them bumped up their Factor IX production enough to go off pharmaceutical Factor IX treatment all together (even with one of the dudes being a marathon runner!), and the two others went from needing treatments several times a week, to only needing a treatment once every couple weeks or so.

Those treatments must be IV, so we are talking about a significant improvement in quality of life here, for these guys, and thats not even factoring in the $$$. A lifetime of these treatments is expensive-- while this kind of gene therapy is one shot (you literally only have one shot-- you will make an antibody response to the virus delivering the functional gene) and thats it. That shot has literally got to cost millions and millions of dollars before it would be as expensive as a lifetime of Factor IX infusions.

From the NEJM editorial:

In the United States and other developed countries, annual costs for a single adult patient of clotting factors for hemophilia are approximately $150,000 for on-demand therapy and $300,000 for prophylaxis,6 which could incur a lifetime cost of over $20 million.


Since the vector is estimated to cost $30,000 per patient, dramatic cost savings have already been achieved.

You know what I was saying yesterday about the rich having access to treatments that people in the developing world cant even dream of? While $30K is by no means 'cheap', it is cheaper, and will hopefully keep getting cheaper upon further refinement. Because this is what happens with Hemophilia B in the developing world:

In developing countries, prophylactic and frequent on-demand therapy is not affordable, and patients still have chronic joint disease and die young.

This treatment is not perfect yet-- but its a huge step in a right direction, and only possible because of viruses.

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One thing that surprises me is that they do not develop an immune response against the factor x. I wonder if they have mutations which produce a non-functional protein, which (in theory) could provide tolerance to the new factor x.


Couldn't the same gene be given to a number of similar vectors that don't have the same immune response, so that multiple treatments becomes a possibility?


Some patients produce a non-functional protein. Others produce no protein. Some of each type were included in the trial (full text available via ERV's link).

I don't know if either type of patient is more likely to develop anti-FIX antibodies. But remember that these patients have typically received large amounts of purified FIX protein by IV infusion throughout their lives. So perhaps even if they initially developed anti-FIX antibodies, the repeated infusions might induce tolerance?

I think it is amazing that injecting a virus into someone's body can act as a cure. However, I do not understand how after a few injections of this people no longer need it. Does this cause the body to begin producing Factor IX on its own or simply provide a supplement? Is it a permanent cure or an ongoing treatment?

Emily@4: it inserts the gene for factor IX into (some of) the patient's cells, so they and their progeny will continue to produce it from then on. So yes, it's a permanent cure.

so they and their progeny will continue to produce it from then on

Their progeny wouldn't have it unless the virus happened to infect one of the patient's germ cells and it developed into a sperm cell. Even then, overproduction of Factor IX could actually be a problem in the children.

By Bill Door (not verified) on 15 Dec 2011 #permalink

Actually, I meant the progeny of the transfected cells. Guess I could have been clearer there.


Perhaps Factor IX as an antigen just isn't very immunogenic so it doesn't usually ellicit an immune response.

Um.. which cells, again? I'm thinking not just any old artery wall / membrane / phagocyte will do... will it?

D'oh! Never mind, 2am question.

I have to wonder if Peutz-Jegher's can be treated in this way.

The lab I worked in during my undergrad did research using lentiviral vectors, and we were able not only (a) give multiple doses without problems and WITH responses in animal models but also, (b)effectively cure the defect using the virus. Which leads me to an inevitable XKCD comic: Because it was SO EXCITING when it worked how we wanted it to and how we expected it to.

(Since I don't post under my real name, if you want a link to the published data, abstracts and papers, as verification that I'm not totally talking out my butt, I could email it to you?) In any case, SCIENCE IS PRETTY FREAKING AWESOME. Viruses doubly so.