Is Treating Hemophilia with Retroviral Gene Therapy Worth the Risk?

Retroviruses are being developed for use as vectors in viral gene therapy for the treatment and possible cure of hemophilia and other genetic diseases. Hemophilia is a genetic disease where mutations in genes for clotting factors disrupt the formation of blood clots, causing excessive bleeding. Current treatments for hemophilia vary depending on the severity of the condition but usually involve injections of clotting factor. While these treatments are effective they are not ideal due to their inconvenience and cost. Injecting oneself or one’s child with clotting factor, which needs to be done three times per week, can be very inconvenient. Additionally the cost of a single treatment of clotting factor can be around $1,700. This inconvenience and high cost are the rational behind developing retroviruses that can be used as gene therapy vectors. In retroviral gene therapy a retrovirus is used to deliver certain genes, in the case of hemophilia genes for clotting factor, to individual’s cells where the virus will then integrate those genes into the host’s DNA. This results in lifelong expression of those genes and hopefully cures the individual of hemophilia or other genetic diseases.

Several major problems arise from using a retrovirus as the gene therapy vector instead of a different virus, most notably retroviral induced mutagenesis. Several clinical trials using retroviral gene therapy have shown great success in treating the disease. However, many of the patients in these clinical trials developed leukemia, which was directly linked to the retrovirus. This brings up the question of whether using retroviruses as gene therapy vectors for treating hemophilia are worth further research.

Some genetic diseases that can be treated by retroviral gene therapy may be considered so terrible it may be worth the risk of getting leukemia. SCID-X1 is an immunodeficiency disorder where the affected individual does not produce T-cells or natural killer cells. These individuals have very weak immune systems and have to live in isolation so no bacteria or viruses can infect and kill them. SCID-X1 is one of the genetic diseases in which retroviral gene therapy has shown great success, however, it is also one of the diseases where in clinical trials a number of the patients developed leukemia because of the retrovirus. This poses the question of whether it is worth treating SCID-X1, a disease in which the common cold would be deadly, with a retrovirus that has the potential to cause leukemia. The answer to this question is up for debate although with advances in cancer treatment it may be worth the risk to cure an individual of SCID-X1. Advances in retroviral gene therapy may eliminate the risk of leukemia however current SCID-X1 patients may die before these advances can be made. In the case of treating baldness with retroviral gene therapy the answer is more clear cut, getting leukemia is not worth having a full head of hair (even if an individual did get a full head of hair from the retroviral gene therapy they would most likely loose it during the chemotherapy treatment for leukemia). In the case of hemophilia, the answer to the question of is treating the disease worth getting leukemia is even less clear cut than the previous two cases. While hemophilia isn’t as deadly as SCID-X1, it has the potential to kill, especially in the severe cases where extreme internal bleeding into joints is likely to occur from simple tasks such as climbing stairs. Its up for debate whether its better to cure hemophilia with retroviral gene therapy and then potentially cause leukemia, which may or may not be treatable, or just stick with current treatments for hemophilia. SCID-X1 and baldness are examples of extremes where taking the risk of retroviral gene therapy is more black and white, hemophilia is in the middle of these two conditions where the risks are in a gray area open for debate. Hopefully someday the choice will not have to be made and improvements in site specific virus integration are made allowing hemophilia patients to be cured of their disease without the risk of getting leukemia.

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