Advanced therapies for the treatment of hemophilia: future perspectives

Antonio Liras,Cristina Segovia,Aline S Gabán

doi:10.1186/1750-1172-7-97

Antonio Liras, Cristina Segovia + Show 1 more

Open Access

https://doi.org/10.1186/1750-1172-7-97

Copy DOI

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.

Highlights

Hemophilia is a recessive X-linked hereditary disorder caused by a deficiency of coagulation factor VIII or IX
Advanced therapies for the treatment of hemophilia In the future, the different types of advanced therapies such as gene therapy, cell therapy and tissue engineering, as well as the more recently developed induced pluripotent stem cells technology, may offer innumerable clinical applications for the treatment of certain monogenic diseases including hemophilia. True as it is that hemophilia is well suited to be treated by advanced therapy protocols on account of its monogenic nature and of the fact that a modest increase in coagulation factor levels is enough to convert a severe into a moderate phenotype, it cannot be forgotten that research in this field is still at an early stage and substantial efforts will have to be made before such therapies can be made readily available to the patients, in terms of safety
Concluding remarks Hemophilia is highly amenable to treatment by protocols based on advanced therapies ―gene therapy, cell therapy, tissue engineering or induced pluripotent stem cell technology—

Summary

Introduction

Hemophilia is a recessive X-linked hereditary disorder caused by a deficiency of coagulation factor VIII (hemophilia A) or IX (hemophilia B). Advanced therapies for the treatment of hemophilia In the future, the different types of advanced therapies such as gene therapy, cell therapy and tissue engineering, as well as the more recently developed induced pluripotent stem cells (iPSC) technology, may offer innumerable clinical applications for the treatment of certain monogenic diseases including hemophilia True as it is that hemophilia is well suited to be treated by advanced therapy protocols on account of its monogenic nature and of the fact that a modest increase in coagulation factor levels is enough to convert a severe into a moderate phenotype, it cannot be forgotten that research in this field is still at an early stage and substantial efforts will have to be made before such therapies can be made readily available to the patients, in terms of safety.

32. Liras A

Findings

38. Matsui H