title: Advanced therapies for the treatment of hemophilia: future perspectives.
abstract: Monogenic diseases are ideal candidates for treatment by the emerging advanced therapies, which are capable of correcting alterations in protein expression that result from genetic mutation. In hemophilia A and B such alterations affect the activity of coagulation factors VIII and IX, respectively, and are responsible for the development of the disease. Advanced therapies may involve the replacement of a deficient gene by a healthy gene so that it generates a certain functional, structural or transport protein (gene therapy); the incorporation of a full array of healthy genes and proteins through perfusion or transplantation of healthy cells (cell therapy); or tissue transplantation and formation of healthy organs (tissue engineering). For their part, induced pluripotent stem cells have recently been shown to also play a significant role in the fields of cell therapy and tissue engineering. Hemophilia is optimally suited for advanced therapies owing to the fact that, as a monogenic condition, it does not require very high expression levels of a coagulation factor to reach moderate disease status. As a result, significant progress has been possible with respect to these kinds of strategies, especially in the fields of gene therapy (by using viral and non-viral vectors) and cell therapy (by means of several types of target cells). Thus, although still considered a rare disorder, hemophilia is now recognized as a condition amenable to gene therapy, which can be administered in the form of lentiviral and adeno-associated vectors applied to adult stem cells, autologous fibroblasts, platelets and hematopoietic stem cells; by means of non-viral vectors; or through the repair of mutations by chimeric oligonucleotides. In hemophilia, cell therapy approaches have been based mainly on transplantation of healthy cells (adult stem cells or induced pluripotent cell-derived progenitor cells) in order to restore alterations in coagulation factor expression.
authors.affiliation: Department of Physiology, School of Biology, Complutense University of Madrid, and Cell Therapy and Regenerative Medicine Unit, La Paz University Hospital Health Research Institute-IdiPAZ, Madrid, Spain. aliras@hotmail.com
authors.forename: Antonio
authors.initials: A
authors.lastname: Liras
authors.forename: Cristina
authors.initials: C
authors.lastname: Segovia
authors.forename: Aline S
authors.initials: AS
authors.lastname: Gabán
mesh_terms: D015316:Genetic Therapy; D006467:Hemophilia A / Q000628:therapy*; D002836:Hemophilia B / Q000628:therapy; D006801:Humans