Wednesday, June 29, 2011

Hope for Hemophilia

So, the following article is all about how gene therapy has the potential to cure Hemophilia. When I read things like this my first reaction is to get excited. I can't imagine how wonderful my life would be without Hemophilia the prospect is just so exciting to me that I don't even let myself believe that a cure is possible. Then the critical side of me kicks in and I think that something like this is too good to be true.  Read for yourself and make your own opinion but I am going to allow myself a few minutes to imagine a world without Hemophilia.

What’s the News: Hemophilia is perhaps best known as a disease of nineteenth-century royalty (specifically, of the oft-intermarried Hapsburgs), but it has evaded our efforts at a cure for thousands of years. And its effects are gruesome: mutations in the gene for a crucial clotting factor mean that victims can rapidly bleed to death from even small cuts.

Now, researchers working with hemophiliac mice have demonstrated a simple and apparently safe technique to swap in a functioning gene, giving hope for a future respite for sufferers of the disease.

How the Heck:

Gene therapy usually involves removing cells from a patient, repairing their damaged genes in a Petri dish, reinserting them, and hoping that they’ll take, a fraught, expensive process. These researchers performed the whole procedure within their mouse subjects, sending in enzymes to snip out the defective gene and a virus carrying a normal gene to replace it.

The mice had been engineered to carry a human gene for hemophilia, and the enzymes and virus had been specifically engineered as well: the enzymes would cut only certain sequences of DNA, patterns that were known to appear on either side of the defective gene, and the virus, which naturally infects the liver cells where the clotting factor is made, would swap in an unmutated gene, instead of the viral genes it would carry in nature.

The treated mice bled for a significantly shorter time than untreated mice and made 3-7% of the normal level of the clotting factor, a level that would result in only mild bleeding in humans. What’s more, even after part of the liver had been removed and allowed to regenerate, the mice continued to produce clotting factor, a sign that the modified cells were passing the normal gene down to their daughter cells.

What’s the Context:
Because the genetic cause of hemophilia is clear, it’s a prime candidate for gene therapy, the process of altering damaged or abnormal DNA to restore normal function.

Gene therapy has shown promise in the lab for treating HIV, Parkinson’s, and even color blindness. Despite early, serious setbacks for gene therapy, clinical trials are now under way for treating a wide variety of genetic diseases.

The type of hemophilia treated here happens to be hemophilia B, which accounts for about 20% cases. But because the therapy replaces the entire gene, it seems likely it would work for the more common hemophilia A as well, which is a mutation in another clotting factor.

Not So Fast:
A serious concern about gene therapy is that enzymes could clip healthy parts of the genome, leading to cancer and other diseases or reactions—researchers have proceeded with utmost caution since children receiving gene therapy for X-linked severe combined immunodeficiency (also known as bubble boy syndrome) developed leukemia as a result of their treatment. One of the reasons scientists perform gene therapy in a Petri dish is so they can check for this by sequencing the genomes of the cells they plan to reinject, as well as watch them for signs of abnormality before putting them back in their patients.

Obviously, it would be much easier if therapy that bypassed this process could be relied upon to not harm the patient, and the fact that the mice have experienced no ill effects over the eight-month period since the treatment is a good sign, as is the fact that the enzymes seem to have snipped only one site beyond than their intended target. But this is a known danger with gene therapy, and researchers will have to show that they can prove the treatment doesn’t cause damage to the rest of the genome.

The Future Holds: This finding is just the first step on a long road to developing a genetic treatment for hemophilia. But it’s a very tidy study, and should prompt much future research into gene therapy.

Reference: Hojun Li, Virginia Haurigot, Yannick Doyon, Tianjian Li, Sunnie Y. Wong, Anand S. Bhagwat, Nirav Malani, Xavier M. Anguela, Rajiv Sharma, Lacramiora Ivanciu, Samuel L. Murphy, Jonathan D. Finn, Fayaz R. Khazi, Shangzhen Zhou, David E. Paschon, Edward J. Rebar, Frederic D. Bushman, Philip D. Gregory, Michael C. Holmes, Katherine A. High. In vivo genome editing restores haemostasis in a mouse model of haemophilia. Nature, 2011; DOI: 10.1038/nature10177.

June 27th, 2011 2:44 PM Tags: gene therapy, Genetic Engineering, hemophilia, Nature (journal)


  1. Thanks for taking this opportunity to discuss this, I feel fervently about this and I like learning about this subject.clinical research in india

  2. I remember my grandfather first telling me about genetic therapy 13 years ago when he first read about it in the NHF mailing he would get from his clinic. He hoped that I would be around long enough to see it happen for my children. Reading this makes me that much more hopeful. There are many things I want to pass down to future generations. Hemophilia isn't one of them.

  3. This is a topic I have been following for some time now. I am planning on some genetic mapping system that actually helps to record the mutations with respect to ancestral genes, and aid gene clipping. Hope it goes well... But in any case, this is a huge breakthrough!

  4. That is so interesting! I would love tohear moreabout it! if there is ever anything you would like to share with the Hemophilia community please let meknow and Iwould be happy to post in on here! Thanks!

  5. Jonathan! I completely agree with you! I think things for the future generation of Hemophiliacs will be much better!! Thank you for reading!

  6. Amiya thank you for reading my blog and taking the time to write! I think this is a great topic and it gives Hemophiliacs a lot of hope!
    please feelto write or share your story with me and I would be happy to place it on my blog!