Hemophilia gene therapy: the first success
The method of gene therapy developed by scientists of the St. Jude Children's Research Clinic, part of University College London and the Royal Free Hospital, has transformed the lives of men with severe hemophilia B. Thanks to the safe and reliable source of blood clotting factor IX introduced into the body, these patients can now lead a much more active lifestyle than earlier.
Hemophilia B is caused by mutations in the X-chromosome gene encoding blood clotting factor IX. Such mutations can lead to a life-threatening decrease in the level of this protein necessary for the formation of blood clots, synthesized by liver cells.
The frequency of the disease, with rare exceptions affecting men, is approximately 1 case per 30,000 people. In severe forms of hemophilia, the level of blood clotting factor IX is less than 1% of normal values, so scratches and bruises in such patients require immediate medical interventions. In addition, painful episodes of spontaneous bleeding can lead to early disability due to joint damage and increase the risk of potentially fatal intracerebral bleeding.
A total of 10 men with severe hemophilia B participated in the study. 7 of them turned to replacement therapy with blood clotting factor IX at least once a week to prevent bleeding. The remaining 3 resorted to injections to stop bleeding or before surgery.
Each of the participants received one of three dosage options for a gene therapy drug containing a modified adenoassociated virus-8 as a carrier of a therapeutic gene encoding clotting factor IX. AAV8 was chosen because it infects human liver cells, but does not embed into their genome and does not cause diseases. The drug was injected once into the peripheral vein of the arm.
After that, an increase in the level of coagulation factor IX was recorded in all patients, which persisted throughout the entire follow-up period (more than 4 years). In general, the frequency of spontaneous bleeding episodes decreased by 90%. At the same time, during the first year after the therapy, the frequency of using replacement therapy with coagulation factor IX decreased by 92%.
In 6 patients who received the maximum dose of the gene therapy drug, the levels of blood clotting factor IX increased from less than 1% of the normal index to 5% or more. As a result, the form of the disease changed from severe to mild severity, which allowed patients to exercise without the use of substitution therapy and increased risk of bleeding. In these men, the frequency of episodes of spontaneous bleeding and the use of coagulation factor IX injections during the first year after therapy decreased by 94%. At the same time, four of them had increased levels of liver enzymes, most likely due to an immune reaction to the introduction of a viral vector. This increase was not accompanied by any symptoms and was stopped by a short course of steroid drugs.
The researchers also assessed the economic effect of the treatment: the total cost of factor IX replacement therapy (and this is a very expensive drug) for the study participants decreased by more than $2.5 million.
Currently, 12 patients are participating in the phase I/II clinical study of the safety and effectiveness of the method. In parallel, work is underway to optimize and study the possibilities of using the viral vector developed by the authors for the treatment of hemophilia A, a similar hereditary disease also characterized by disorders of the blood clotting system.
Article by Amit C. Nathwani et al. Long-Term Safety and Efficacy of Factor IX Gene Therapy in Hemophilia B is published in The New England Journal of Medicine.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of University College London:
Gene therapy provides safe, long-term relief for patients with severe hemophilia B.
20.11.2014