GMO Virus: Long-term success treating Hemophilia B

One of my favorite stories is the tale of a GMO virus deployed to treat Hemophilia B:

Gene therapy for Hemophilia B

... 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 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.

Okay, I wrote that post late 2011.

They published an update late last year:

Long-Term Safety and Efficacy of Factor IX Gene Therapy in Hemophilia B

When you are treating a genetic disease with gene therapy, the point is to treat them once and be done with it. Broken gene-->Fix the gene--> DONE! And its reeeeeally important that everything works well the first try, because second/third/fourth tries with GMO viruses complicate things.

See, your body doesnt 'know' the GMO viruses are there to help. So your immune system sees the GMO virus and generates antibodies to kill those viruses the next time they see it. The more times you have to administer a GMO virus, the more antibodies a person will make, the less likely second/third/fourth doses will do a damn thing.

So what happened in these patients up to four years after they were treated? How good was that one dose?

They followed the six from the previous study, plus another four (who got the 'high' dose of virus), who all got one dose of Adenovirus-Associated Virus-8, genetically modified to deliver a functional copy of Factor IX.

The treatment was safe-- There were no terrible side effects. Some had annoyed livers right at treatment, but prednisone fixed that. No long-term problems.

And boy, did this GMO virus help long-term!

The patients were nowhere near 'normal' levels of Factor IX, BUT, the viruses got enough functional Factor IX floating around to:

The annual amount of factor IX concentrate that was administered to all 10 patients dropped from a median of 2613 IU per kilogram (interquartile range, 1671 to 4513) in the year before vector infusion to 206 IU per kilogram (interquartile range, 79 to 948) in the year after vector infusion (P=0.002), a relative reduction of approximately 92%. In the high-dose group, the amount of factor IX concentrate that was used dropped from a median of 2613 IU per kilogram (interquartile range, 1627 to 3487) to 92 IU per kilogram (interquartile range, 38 to 395), a relative reduction of 96% (P=0.03). Despite this decline in factor use, the annual number of bleeding episodes for the entire cohort of 10 patients decreased from a median of 15.5 bleeding episodes (interquartile range, 10.3 to 19.3) 1 year before vector infusion to 1.5 episodes (interquartile range, 1.0 to 4.0) in the year after vector infusion, a relative reduction of 90% (P=0.009). When only patients in the high-dose group were considered, the annual number of bleeding episodes decreased from a median of 16.5 episodes (interquartile range, 12.5 to 27.0) to 1.0 episode (interquartile range, 0.8 to 2.5), a relative reduction of 94% (P=0.03).


The overall reduction in the amount of factor IX concentrate that was administered over the duration of the study was more than 3 million units, resulting in a financial savings of more than $2.5 million based on 2014 prices.

The amount of therapeutic Factor IX these patients needed (on average) dropped from 2613 IU/kg to 206. The people who got the 'high' dose of virus dropped that down to 92 IU/kg. They went from 15-16 'bleeding episodes' a year, to one.


And not only were these individuals lives improved, not being shackled to a hospital for IV treatments of Factor IX, not having regular 'bleeding episodes', their ability to live without these treatments saved $2.5 million.

'GREAT JOB!' to the scientists and physicians involved with this, and I hope they get this therapy to more folks ASAP!

More like this

On ERV, Abbie Smith provides an update on a pioneering treatment for hemophilia that uses viruses to insert missing genes in a patient's DNA. Hemophilia results from from the mutation or deletion of a gene that makes a blood clotting agent called Factor IX; without it, hemophiliacs are at risk for…
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…
When youre trying to cure a genetic disease with a genetically modified virus, you dont have to get a perfect score. You dont have to cure everyone in the trial. You dont even really have to cure them-- Just make their lives a little easier, making it so that they can skip a few invasive procedures…
So what do you do after you use a genetically modified virus to treat-->functionally cure Hemophilia B? Why, use a genetically modified virus to treat-->hopefully functionally cure Hemophilia A, of course! Generation of an optimized lentiviral vector encoding a high-expression factor VIII…

Thanks for the heads-up. This is excellent work that our scientist and physicians are doing. but will this treatment be available to everyone despite their economic situation or it will be more available to those who are rich or its its going to be made affordable enough for everyone?

By u14241308 M Ma… (not verified) on 14 Apr 2015 #permalink

i agree .. this treatment would be released to other people who are suffering from this disease..,, do you think the treatment will be free?. wont it be costly for developing and undeveloped countries? which will not be fair for those who are sick but have no money .14047366

By Tshikovhi elelwani (not verified) on 14 Apr 2015 #permalink

I do not think that the treatment will be free because;
it is a new treatment so governments will not endorse the treatment especially in developing countries, it is not a major problem like AIDS or Ebola for example as it only affects a small population of people, lastly the treatment is still in trial phase.

By Casey Gill (not verified) on 15 Apr 2015 #permalink


By Casey Gill (not verified) on 15 Apr 2015 #permalink

Wow! Really interesting stuff. My brother is a haemophiliac and this would really save my family from the stress and hospital visits if he received this treatment.

By Vanessa de Jesus (not verified) on 15 Apr 2015 #permalink

It is always such a pleasure to see other people's hard work pay off, well done to those scientists and physicians. I think that, since Hemophilia b is such a rare disorder to be born with, the treatment will be costly. I also think that hospitals should think of having some kind of "waiting list" for the treatment that can cater for those who cannot afford , judging by how serious their condition is.

By Angelicah Kiggundu (not verified) on 15 Apr 2015 #permalink

RE: #6

I agree that hospitals should having some kind of waiting list for the treatment for those who need it and cannot afford it, however, how do the hospitals decide who needs the treatment more than the next person?? Correct me if I am wrong but doesn't Haemophilia B affect males all in the same way? 15083820

By Casey Gill (not verified) on 15 Apr 2015 #permalink

considering how successful genetic modification has become, do you think that scientist will be able to cure genetic diseases like huntington's completely by stopping nerve cell degeneration?

By Damean Billson (not verified) on 15 Apr 2015 #permalink

That is remarkable! This treatment will without a doubt make a difference in many people's lives and agree that it should be made available especially in under-developed countries. The success of this treatment definitely shows the great potential that genetic modification has in possibly treating other genetic diseases.

By Refiloe Motsat… (not verified) on 15 Apr 2015 #permalink

Wow! I think that it is outstanding that they have managed to find a treatment. I agree with the comments above that it will most likely not be free or inexpensive as the disorder is quite rare and as we have seen, most other rare illness treatments are very expensive. I think that there should be awareness and funding from the government so people in need can receive the treatment.

By Jenna Rheeders… (not verified) on 15 Apr 2015 #permalink

This is such a remarkable discovery... A step forward in the genetic world.

By Bagcinile (not verified) on 15 Apr 2015 #permalink

RE: #6

Yes, I definitely think that with the advancment of genetic modification scientists and physicians will come up with a cure for Huntington’s Disease. I read recently that, The National Institute of Neurological Disorders and Stroke, have performed and are still in the process of performing several clinical trials that attempt to control and eventually cure the disease by hindering the progressive break down of nerve cells.

By Casey Gill (not verified) on 15 Apr 2015 #permalink

This is so good to hear. Medicine and science are really making remarkable headway. I just want to know are there any other forms of hemophilia and do they have a miracle drug too?

Hats-off to the great scientific minds behind this effective and easily admnistered treatment. It will definitely improve the quality of life for all those afflicted by this unfortunate condition.

This is really amazing. i have a dear friend who suffers from this condition and i am not sure if he knows about this treatment, and its great long term effects, but i cannot wait to tell him.

I'm constantly amazed by the heights human intelligence and ability continues to ascend to! This is another giant leap for mankind. Governments and corporates must continue supporting and enabling scientific research. I'm so pleased for hemophiliacs and the positive difference this virus is going to make in their lives. Nicely done indeed....

From the positive results of this therapy, what is the turnaround time to implementation in mainstream health practices. Are there any certifications that need to be "checked off the list" before implementation ?

By Maleho Sadiki (not verified) on 15 Apr 2015 #permalink

A well thought research since Hemophilia B is a difficult disease to treat and is potentially life threatening. My concern is the use of prednisone, I want to know how long were they on it because since is a glucocorticoid and prolong use can lead to gastric ulceration which may lead to other complications.

By Nehemia Mokgaliphe (not verified) on 15 Apr 2015 #permalink

Congratulations are in order for the remarkable work these scientists have done. You mentioned in the post that some patients experienced minor complications like irritated livers would you care to explicitely elaborate on that, how severe were these irritations?

By Nomaswazi Mase… (not verified) on 15 Apr 2015 #permalink

Interesting work indeed. Can I please have a link to journals or any online posts by these scientists following this particular research, I would like to read further about this.

By Masanabo Prudence (not verified) on 15 Apr 2015 #permalink

I am wondering about the virus. Was this virus once one that caused people to be sick or is it just called a virus because of its characteristics?

By Monique 15028382 (not verified) on 16 Apr 2015 #permalink

This is awesome that people affected with this genetic disorder have the possibility of cured and living normal lives. For how long was the prednisone administered and why were their livers annoyed?

By Z Manzini (u15… (not verified) on 16 Apr 2015 #permalink

Although Haemophilia B is thought to be not a major disease as Ebola it can be life threatening. Thumbs up to the scientists that found the therapy, not only did they achieve in helping improving peoples lives but it saved a huge amount of COST on treatments which should give less reasons for governments to not offer the therapy to the poor.
I presume the 10 patients went through extensive clinical and laboratory monitoring and showed great improvements with less side effects why is the therapy still on trial and not dispatched the the majority in need.

By R.S Sitwala u1… (not verified) on 16 Apr 2015 #permalink

The work scientists do is remarkable. Shows how one does not necessarily have to be a medical doctor in order to improve lives of people.

It does ,however,leave me a bit to confused. Does the treatment of Haemophilia destroy the recessive trait in affected males to such an extent that when they have children, they have no chances of having Haemophilia?
Could it not be better to destroy the recessive trait in carrier parents, than to have to impose treatment to affected children?

By Sbongumenzi Qwabe (not verified) on 16 Apr 2015 #permalink

Monique; All viruses cause people to exhibit some "sickness" symptoms to some extent. Swollen lymph nodes, for instance, are symptomatic of the ways your body fights the virus.

Tshikovhi; Funny thing about viruses; they tend to propagate freely. A virus of a certain type could be made to infect an entire quarantine-room full of people, through sneezing or other transmission vectors. I imagine it would be important to keep them quarantined, however, to prevent the virus from mutating. Then we'd have another problem on our hands entirely...

The discovery of the Adeno-Associated virus-8 to save lives of people with Haemophilia can be said to be one of the best discoveries in years.It is a new discovery but yet working miracles, it is said that it might be costly but i think health organisations and goverment could work together to making this treatment available to every individual.Thank you to the hard working scientists who aim at making a difference in people's lives.Is this treatment available in all countries or only in specific countries?

By Lungile U15324959 (not verified) on 17 Apr 2015 #permalink

The strides being made in medicine are amazing. Such beneficial medicine should not be patented so as to help those who cannot afford it, before this is done, the small print, such as the minor complications mentioned should definitely be fixed , gene therapy focuses on biological functions crucial to human survival and side effects that affect that can be fatal.

By Leslie u14218594 (not verified) on 17 Apr 2015 #permalink


I don't not think that the recessive trait, Haemophilia can be destroyed, it can only be treated like with all other genetic disorders. I do agree with you however ,that it would be better to destroy the disease all together so that the parents do not produce offspring who suffer from the disease. I am certain destroying the recessive allele of Haemophilia and other genetic disorders are going to be the next big advancement in medicine.

By Casey Gill (not verified) on 17 Apr 2015 #permalink

This thus shall save more male lives, i mean haemophilia is n issue especially among male people and it i affecting th generation to come after the male. the dicovery of the agent will thus help stop this.

It is heart warming to see that there is studies being done on this virus because although it is a rare disease it can take over someone's life completely. Well done to the scientist and physicians who initiated and succeeded in this study to treat haemophiliacs.

By Carike Odendaa… (not verified) on 17 Apr 2015 #permalink

I doubt that the treatment would be effective over 10 years. it is too early to claim that the treatment is long term. There wouldn't be enough healthy genes in the first treatment to flush out the mutated genes that is why treated hemophiliacs will still experience bleeding (although not as often). Over time the percentage of mutated genes would begin to increase again.

By Guy Schiever (not verified) on 17 Apr 2015 #permalink

This is an excellent treatment that has been developed by scientists as it improves the lives of people suffering with Hemophilia.
But what would the cost of this treatment be and would these costs be reduced for people who receive little - no income?

By Jovishka Maharaj (not verified) on 18 Apr 2015 #permalink

Well done to the scientists for making a progressive breakthrough in medicine. Hope this changes the lives of people.

It is amazing to hear about the great discoveries by scientists in the medical field. If this treatment is sustainable, it could improve and lengthen the lives of many who are affected by the disease. Haemophilia is a genetically inherited disease and if cured, can decrease the risk in offspring. However the long term effects of GMO's are unknown and I sincerley hope that this treatment is resilient.

Congratulations to the scientists for such a great discovery. We were told that GMOs are harmful but this counteracts all other ideas. Let's hope for the best in the future.

This means great things for low income populations such as india. The Prevelance rate in India is up to 1: 10000 now and continues to rise. Lower costing methods like this will pave a way for more therapies to be created and established in countries such as India and give an option to people who couldnt usually afford any treatment.

Can we really say that people of low income will be able to access treatments like this ? The research is extremely positive but i do feel that many affected to people will continue to suffer in countries without free medical care

This goes to show how one concept can be bad in one aspect but good in another. Out of curiosity, what would the implications be on a patient who would need a mechanical heart valve to replace their own faulty heart valve and also happens to be a haemophiliac?

Well done to the scientists who have worked so hard on finding the treatment of Hemophilia B.This means that the male generation can still go on with people being treated with this disease.u14231591

By Nhlamulo Hobyane (not verified) on 19 Apr 2015 #permalink

This is phenomenal. Tremendous strides are being made

By H Gregory (not verified) on 19 Apr 2015 #permalink

WOW. Never thought its possible .this is exactly what i want to do. MEDICAL RESEARCH thanks for the encouragements ....

RE: #38

Haemophilia patients are more likely to have blood transfusions, increasing their chance of receiving contaminated blood.

By Casey Gill (not verified) on 20 Apr 2015 #permalink

This able will same Hemophilia B patients lot of time as they will be no constant visitation of hospitals, this is a wonderful.

AFAIK, gene therapy (as being trialled by the NHS in the UK) is currently still pretty pricey - the savings from reduced treatment needs probably come pretty close to the cost of treating in the first place. However, once they get into economies of scale, I bet the cost of the gene therapy will drop and then you'll see NICE or similar start to approve treatments like this. That's going to be a great moment. Here's hoping this treatment can be equally successfully adapted for other common diseases like CF.