Treating Haemophilia A with Gene Therapy

Haemophilia is a condition that affects the ability of the blood to clot when you are wounded. There are two main types of Haemophilia: Haemophilia A and Haemophilia B. Each result from the body being unable to produce a specific clotting factor due to inheriting a faulty x chromosome; which does not possess the gene needed to produce the correct clotting factor, so the body doesn’t have the instructions it needs to produce them.

This means haemophilia is more common in men than women, as men only inherit one x chromosome, whereas women inherit two. So women are more likely to be ‘carriers’ of the disease, with the ability to pass the disease onto their children, without displaying symptoms themselves. The symptoms of haemophilia can include bruising, joint bleeds and muscle bleeds.

The main focus of this article will be on Haemophilia A. In haemophilia A, the clotting factor the body is unable to produce is clotting factor VIII. Previously, the only available treatment for this would be an injection of a manufactured version of the clotting factor into the blood every other day for life.

Haemophilia is a chronic condition and there is currently no cure. Side effects of these clotting factors include skin rashes, headaches and fevers.

However, this could soon all change. Trials for a new gene therapy to treat haemophilia A have been carried out at Barts and the London school of medicine and dentistry, and the results have been promising.

Researchers used an Adeno-associated virus as a vector to insert the missing human factor VIII gene into cells in the liver, which would be able to use the gene so the body would be able to produce its own clotting factors.

Adeno-associated viruses (AAV) are single-stranded DNA viruses and are used as they are non-pathogenic to humans, so usually don’t trigger an immune response from the body, enabling the virus to deliver the gene safely to the body’s cells.

The gene was given to nine men with severe haemophilia A. The participants were given varying doses and their progress was followed for the next 52 weeks. In 6 out of 7 of the patients who were given a high dose of the gene, by the end of the 52 weeks, their body was able to produce normal levels of the clotting factor, meaning they no longer had to rely on almost daily injections.

The patients were then followed over the next three years to see if their clotting levels remained stabilised. The researchers found that those who had received the high dose of the gene had ceased their use of clotting factor injections completely and they no longer had bleeding in their major joints. In the first study, patients were initially found to have elevated levels of a particular liver enzyme, however, after being followed for three years there were no persistent changes in liver-function that were observed.

While this study was small, and gene therapy is still only in its infancy, such studies provide hope that one day the use of life long injections to treat haemophilia will be eliminated.

References

Milad Rouf Final Year Medical Student, Cardiff University.

Lee, E., Guenther, C. and Suh, J., 2018. Adeno-associated virus (AAV) vectors: Rational design strategies for capsid engineering. Current Opinion in Biomedical Engineering, [online] 7, pp.58-63. Available at: [Accessed 7 July 2020].

nhs.uk. 2020. Treatment For Haemophilia - NHS. [online] Available at: [Accessed 7 July 2020].

Pasi, K., Rangarajan, S., Mitchell, N., Lester, W., Symington, E., Madan, B., Laffan, M., Russell, C., Li, M., Pierce, G. and Wong, W., 2020. Multiyear Follow-up of AAV5-hFVIII-SQ Gene Therapy for Hemophilia A. New England Journal of Medicine, [online] 382(1), pp.29-40. Available at: [Accessed 7 July 2020].

Rangarajan, S., Walsh, L., Lester, W., Perry, D., Madan, B., Laffan, M., Yu, H., Vettermann, C., Pierce, G., Wong, W. and Pasi, K., 2017. AAV5–Factor VIII Gene Transfer in Severe Hemophilia A. New England Journal of Medicine, [online] 377(26), pp.2519-2530. Available at: [Accessed 7 July 2020].