Gene therapy shown to assist
blood clotting in haemophilia

An experimental gene therapy technique boosted the production of a vital blood clotting factor in six people with haemophilia B, according to new research published online 10 December 2011 in the New England Journal of Medicine. The therapy could give patients a long-term solution for preventing prolonged bleeding episodes and spontaneous bleeding.

Haemophilia B patients are unable to produce enough human clotting factor IX, also referred to as FIX, which is essential for normal blood clotting. Liver cells are the only cells in the body capable of producing a form of factor IX that is active in the clotting process.

In the study researchers joined the FIX gene to a virus that targets liver cells. This allowed the normal FIX gene to be delivered using intravenous infusion to the liver cells of patients with haemophilia B. The infusion allowed the patients to produce more FIX.

Researchers from the University College London Cancer Institute, and St. Jude Children’s Research Hospital, Memphis, in the US, led a team that examined the effects of delivering the FIX gene to patients. Scientists inserted the FIX gene into a virus, which served as the delivery vehicle for the gene therapy.

The researchers studied six people with severe haemophilia B who were producing clotting factor IX at less than 1% of normal levels before receiving the gene therapy. Prior to enrolling in the study, participants were receiving the standard treatment for severe haemophilia B of infusions of manufactured FIX several times a month.

The FIX gene was packaged in a modified adeno-associated virus, AAV8, which targets liver cells. After receiving the FIX gene therapy, each participant produced FIX at between 2% and 11% of normal levels. In the short-term follow-up period (six to 16 months), four of the six participants no longer required FIX infusions for routine bleeding. The other two participants required FIX infusions less frequently than before the study.

The unique feature of this approach is the use of AAV8 to deliver the gene to the appropriate cells. If future studies show that immunologic or other factors do not limit its long-term effectiveness, people with haemophilia B could produce their own FIX and potentially avoid reliance upon FIX infusions. While more work is needed, these results are more promising than prior attempts at gene therapy for the haemophilias.

Haemophilia B is less common than haemophilia A, a deficiency of clotting factor VIII. About 1 in 5 haemophilia patients has haemophilia B, while the other four have haemophilia A. Haemophilia is an inherited condition that affects men more frequently. Worldwide, about 1 in 5,000 men are born with haemophilia A and 1 in 25,000 men are born with haemophilia B each year.

Organisations in the United Kingdom that provided funding for this research included: the National Health Service; the National Institute for Health Research; the Department of Health; and the Royal Free Hospital. Funding sources in the United States included: the Howard Hughes Medical Institute; the ASSISI Foundation of Memphis; and the American Lebanese Syrian Associated Charities.

 Date of upload: 21st Jan 2012


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