Gene therapy and Haemophilia cure-A reality now

Hi everyone, long time no see. I have been spending my time revising for the ukcat and doing so many other things such as volunteering and mentoring students for the Generation Bridge Project. Today id like to share a research paper I submitted to the British Society of Gene and Cell Therapy.

Haemophilia A is an X linked bleeding disorder caused by genetic mutation thus resulting in an insufficient protein  that is required for blood clotting.1 Factor VIII deficiency in Haemophilia A results in frequent and severe bleeding tendency that can be life threatening. Hemophilia A occurs in 1 of 5,000 male births and estimates suggest that there are more than 2,000 patients of severe Haemophilia A in the United Kingdom. Severe Haemophiliacs virtually don’t have any factor VIII for the blood to clot. 1,2,3

Treatment of Haemophilia A has come a long way. Starting with snake venoms in 1930 for blood clotting, treatment options moved to fresh frozen plasma in 1960. In 1992, the first recombinant factor VIII product was approved in USA by the Food and Drug Administration (FDA).4 The present treatment involves lifelong injections of missing factor VIII concentrates several times per week in order to prevent bleeding.2

Scientists have always fancied to find gene therapy as a cure for haemophilia. The basic concept is to replace the mutant gene with a healthy copy of gene. After many years of research the gene therapy is about to come a reality. The latest trial has been carried out by researchers including those from Cambridge University Hospital, Imperial College London, Barts and from BioMarin Pharmaceutical in the US, which is developing the gene therapy. The eventual aim of treatment is to replace defective gene sequence with a corrected version that will trigger the manufacturing cells to release therapeutic factor VIII into the circulation of haemophilia patients thus curing the disease for lifetime of the patient. The new treatment tactics employs an adeno-associated virus, modified forms of the virus to deliver missing sections of DNA, but the virus itself doesn’t cause any symptoms. The adeno-associated virus AAV serotype transfers missing DNA to the liver cells so they could start making factor VIII.1 This new treatment is a single injection process. This clinical trial study is basically a dose escalation study, where people were given sequentially increased doses of a treatment to be sure it’s safe before the next patient is given a higher dose. Researchers recruited 9 men with haemophilia A. The all participants had their regular factor VIII injections suspended for the trial, although they could use and benefit from factor VIII if they experienced any bleeding .The first person was given a low dose, and the second person an intermediate dose. The third participant received a higher dose, and when that was shown to work without any problems, another 6 men were given the higher dose.
The 2 men who had low or intermediate doses of gene therapy there was a little change in the levels of factor VIII, they continued to experience bleeding episodes, and were required to continue factor VIII injections. Among the 7 men who received the higher dose, all had levels of factor VIII of more than 5 IU per decilitre by 9 weeks after gene therapy. In 6 patients factor VIII levels plateaued to a normal value (more than 50 IU per decilitre) and remained at that level a year after gene therapy. The average number of bleeding events dropped from 16 before therapy to 1 after therapy. None of patients developed antibodies against the factor VIII and all of them were able to stop injecting factor VIII. Those participants who had high dose therapy all showed an increase in a liver enzyme up to 1.5 times the normal level but they didn’t report having any symptoms from this increase, and liver cells continued to produce factor VIII.5.6.7

We have seen enormous progress in field of gene therapy for Hemophilia A and results are impressive.8 This gene therapy is one off treatment for entire life time and could change the lives of thousands of people around the globe who rely on factor injections as often as other day. The results from this early trial of a therapy is a remarkable success however it may take some time   before the treatment is available widely. Results need verification in much larger groups of people as well as in children. We also need safety data in these large groups to be sure that the treatment doesn’t cause serious health problems especially in the longer term. Economics is another challenge as costs of new drugs tend to be alarming but there is no doubt that the future of Haemophilia patients is brighter.


1- David S and Jay NL. Gene therapy for haemophilia: Prospects and challenges to prevent or reverse inhibitor formation. Br J Haematol. 2012 Feb; 156(3): 295–302.

2- Arthur W. et al. Gene Therapy for Hemophilia.



5- Savita R et al. AAV5–Factor VIII Gene Transfer in Severe Hemophilia A. N Engl J Med 2017 Dec; 377:2519-2530.



8- Samuel LM  and Katherine A H. Gene therapy for haemophilia. Br J Haematol. 2008 Mar; 140(5): 479–487.

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