动物实验,血友病 z-bo 2020-09-10 371

　　Hematology researchers have further improved their views on how to use the emergency treatments currently used to control bleeding in patients with hemophilia as preventive treatments. Animal experiments have the potential to develop antibodies against current standard maintenance therapies, and lay the foundation for new therapies for hemophilia patients who need "bypass" therapy as needed.

　　Fisher is a hematology researcher at the Raymond G. Perelman Cell and Molecular Therapy Center at the Children’s Hospital of Philadelphia. “Patients with anticoagulant factor antibodies are usually used to treat hemophilia and must be complicated. Treatment. “Another factor VIIa can be used in bleeding. After clotting the blood, we do not know that the target level of circulating factor VIIa can prevent bleeding before bleeding. The target level of the new preclinical outcome activity is the first to show that it can be prevented. "

　　Margaritis pointed out that the threshold of circulating factor VIIa to prevent animal bleeding events will be included in future patient clinical trials. I tell you yes. The research team announced the results on Blood Advances on February 12, 2019. Hematopoietic system disease is an inherited bleeding disorder, in which genetic mutations can impair the blood's ability to clot. If it is not fatal, severe hemophilia can cause pain, often leading to spontaneous bleeding and joint damage. The disease usually occurs in two types: hemophilia A and hemophilia B. The difference is that natural clotting factors are affected. A deficiency or deficiency of blood factor VIII can cause hemophilia A, and hemophilia B can damage factor IX. The management of hemophilia may include a series of measures, as well as the use of blood factors by clinicians. For many years, the standard method of treatment has been prophylactic and frequent intravenous injections of factors as needed. However, one-third of hemophilia A patients and as many as 5% of hemophilia B patients produce inhibitors through this factor replacement therapy, so the treatment is ineffective. In a long-term procedure called "induction of immune tolerance", factors are repeatedly injected to eliminate inhibitors, but more than 40% of patients cannot be treated. For relapsed patients, the only option is to implement a bypass strategy, infusion of other compounds that may form blood clots: activated recombinant factor VIIa, activated prothrombin complex or recently approved. FDA-approved antibody whole blood friend patient A. "Factor Villa is still widely used, but it is not yet clear about the level of Factor Villa for prevention and safe use. Margaret said. Marguerite and her colleagues have been Gene transfer has been extensively studied in animal models (mice and dogs). These experiments generate factor villas and provide modified DNA containing coding instructions to reduce bleeding events. The current study uses genetically designed hemophilia A rats Model to experience bleeding events. Pharmaceutical company NovoNordisk A/S provides patients with the main source of bypass reagent VIIa.

　　The research team used adeno-associated virus (AAV) as a vector to deliver the rat factor VIIa gene. The gene expression factor Vila has a dose-dependent effect and mimics the preventive effect. The factors that reached a certain blood flow level reduced the bleeding of hematopoietic A rats, and completely eliminated these bleedings at a higher level.

　　"This is the first time we have used factor villa threshold levels for prevention," Margaritis said. "Factor VIIa should be suitable for hemophilia A and hemophilia B because it avoids the need for factor VIII or IX. In addition, it is effective regardless of the presence of inhibitors in the blood. Margaret’s study The next step is to convert the rat threshold levels to human levels and use this information as the basis for clinical trial methods.