Hemophilia gene therapy: success confirmed

Gene therapy cured hemophilia for the first time

Ksenia Malysheva, Naked Science

Gene therapy was used for the first time to treat hemophilia; one intravenous injection of harmless viruses carrying the plasma factor IX gene was enough to stop bleeding, and in some cases even refuse injections of clotting factors.

An international team of scientists has completed the first experiment on gene therapy of hemophilia B, a rare blood clotting disorder due to a recessive mutation of the X chromosome gene encoding plasma factor IX. In healthy people, plasma factor IX is produced in the liver and from there enters the blood, where its concentration is 4-5 micrograms per 1 ml of plasma. With hemophilia B, the concentration of factor IX drops to 2% of the norm, which leads to a violation of the first phase of blood clotting, due to which the slightest mechanical damage leads to the formation of hematomas, hemorrhages in the joints and late bleeding.

Hemophilia B is treated symptomatically: when bleeding occurs, external or internal, antihemophilic serum with factor IX and complexes of other blood factors are injected. Without these injections, even a small cut, bruise or spontaneous internal bleeding (and they are not uncommon in hemophiles) can lead to serious blood loss and even death.

In an experiment described in an article published in The New England Journal of Medicine (Hemophilia B Gene Therapy with a High-Specific-Activity Factor IX Variant), ten hemophiliac patients were injected with viral vectors carrying a promoter and a transgen encoding factor IX. Once in the liver, the vectors embedded a promoter and a transgen of a particularly active version of factor IX into the patient's liver cells; this allowed reducing the dose of viral vectors and avoiding an immune response.

18 months after the injection, the liver of the experimental participants produced 34% of the normal amount of factor IX; for nine out of ten patients, this was enough to stop bleeding; eight patients no longer needed regular injections of factor IX.

Graph from an article in NEJM – VM.

No side effects were observed in 8 out of 10 patients; in two cases, in response to the injection of viral factors, the production of some liver enzymes increased, but it was returned to normal with steroid drugs.

In previous experiments, injections of viral vectors or transplantation of genetically modified cells with a normal factor IX gene did not give positive results: in some cases, GM cells caused a strong immune response, in others, the cells did not produce factor IX in sufficient quantities. (In fact, a year and a half ago, the same group of researchers reported on the treatment of three volunteers with approximately the same results – VM.)

Hemophilia B affects about 20% of all patients with blood clotting disorders; scientists are looking for a way to cure a more common version of the disease, hemophilia A, associated with congenital deficiency of blood clotting factor VIII.

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