Semin Thromb Hemost 2019; 45(07): 743-750
DOI: 10.1055/s-0039-1688445
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Gene Therapy: Paving New Roads in the Treatment of Hemophilia

Gabriela G. Yamaguti-Hayakawa
1   Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil
2   IHTC Hemophilia Unit Cláudio Luiz Pizzigatti Corrêa, INCT do Sangue Hemocentro UNICAMP, University of Campinas, Campinas, São Paulo, Brazil
,
Margareth C. Ozelo
1   Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil
2   IHTC Hemophilia Unit Cláudio Luiz Pizzigatti Corrêa, INCT do Sangue Hemocentro UNICAMP, University of Campinas, Campinas, São Paulo, Brazil
› Author Affiliations
Funding Dr. Yamaguti-Hayakawa reports personal fees and nonfinancial support from Roche outside the submitted work. Dr. Ozelo reports grants from BioMarin, Pfizer, during the conduct of the study and grants from Novo Nordisk, Shire, Bioverativ, and Roche outside the submitted work.
Further Information

Publication History

Publication Date:
16 May 2019 (online)

Abstract

Hemophilia is a monogenic disease with robust clinicolaboratory correlations of severity. These attributes coupled with the availability of experimental animal models have made it an attractive model for gene therapy. The road from animal models to human clinical studies has heralded significant successes, but major issues concerning a previous immunity against adeno-associated virus and transgene optimization remain to be fully resolved. Despite significant advances in gene therapy application, many questions remain pertaining to its use in specific populations such as those with factor inhibitors, those with underlying liver disease, and pediatric patients. Here, the authors provide an update on viral vector and transgene improvements, review the results of recently published gene therapy clinical trials for hemophilia, and discuss the main challenges facing investigators in the field.