Основные направления по разработке и модификации препаратов для лечения гемофилии

Abstract

The basic method of the treatment of haemophilia A and B is the replacement therapy by preparations obtained from plasma of donors, or by recombinant DNA technology. Among the major shortcomings of unmodified drugs VIII and IX factors should be allocated between the low time circulation of the drug in the body of the patient and the delivery of antibodies (inhibitors) to a protein preparation that significantly reduces their effectiveness. The improvement of the efficiency and safety of recombinant preparations is achieved by removing B-domain of factor VIII molecule, pegylation or development of preparations of fusion proteins (fusion molecules of the preparation to the albumin or Fc-fragment of IgG). These modifications, especially, enhance the stability of the molecule of the active substance to increase half-life and reduce immunogenicity of recombinant products. Replacement therapy with traditional preparations in hemophilia patients delivering antibodies (inhibitors) to the preparation is ineffective. Taking this into account, in recent years, new preparations have been developed for alternative approaches treatment of hemophilia. There were developed the preparation based on bispecific monoclonal antibody mimicking the function of factor VIII; monoclonal antibodies and aptamer blocking the activity of tissue factor pathway inhibitor, and the preparation based on antisense oligonucleotide blocking mRNA responsible for the synthesis of antithrombin III. The main advantage of these new formulations is that they do not cause the production of antibodies to coagulation factors and so can be used for the treatment of patients with inhibitors in blood.