Establecimiento de protocolos de terapias avanzadas, génica y celular, para el tratamiento del déficit de factor v y factor viii de la coagulación

Abstract

This Doctoral thesis, titled Establishing advanced gene and cell therapy protocols for the treatment of coagulation factor V and factor VIII deficiencies, is an attempt to lay the foundations for the development of an effective, specific, and potentially curative treatment of those two rare hemorrhagic conditions based on advanced cell and gene therapies. Rare or uncommon diseases are those whose prevalence is below 1 case per 2000 in the general population. Many of these conditions are misdiagnosed and lack a specific and effective treatment. That is why research and the ensuing development of new treatments is so crucial. Rare congenital coagulopathies, such as factor V and factor VIII deficiencies, are characterized by bleeding episodes, which may be more or less intense as a function of the levels of coagulation factor activity present in plasma. Fresh-frozen plasma, often used to treat patients with factor V deficiency, is not usually very effective and is typically administered on demand depending on the severity of the specific bleeding episodes. Factor VIII concentrates, for their part, are administered prophylactically via the intravenous route two or three times a week in patients with factor VIII deficiency. As these treatments are tedious and often result in poor patient adherence, it is of the essence to develop a long-term “curative” treatment capable of either normalizing levels of the deficient factor on an ongoing basis or correct the patient’s genetic defect. Such curative treatments can only be developed by recourse to the new advanced therapies...