title: Hemophilia A: an ideal disease to correct in utero.
abstract: Hemophilia A (HA) is the most frequent inheritable defect of the coagulation proteins. The current standard of care for patients with HA is prophylactic factor infusion, which is comprised of regular (2-3 times per week) intravenous infusions of recombinant or plasma-derived FVIII to maintain hemostasis. While this treatment has greatly increased the quality of life and lengthened the life expectancy for many HA patients, its high cost, the need for lifelong infusions, and the fact that it is unavailable to roughly 75% of the world's HA patients make this type of treatment far from ideal. In addition, this lifesaving therapy suffers from a high risk of treatment failure due to immune response to the infused FVIII. There is thus a need for novel treatments, such as those using stem cells and/or gene therapy, which have the potential to mediate long-term correction or permanent cure following a single intervention. In the present review, we discuss the clinical feasibility and unique advantages that an in utero approach to treating HA could offer, placing special emphasis on a new sheep model of HA we have developed and on the use of mesenchymal stromal cells (MSC) as cellular vehicles for delivering the FVIII gene.
authors.affiliation: Regenerative Medicine, Wake Forest Institute for Regenerative Medicine Winston-Salem, NC, USA.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Porada
authors.affiliation: Regenerative Medicine, Wake Forest Institute for Regenerative Medicine Winston-Salem, NC, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Rodman
authors.affiliation: Regenerative Medicine, Wake Forest Institute for Regenerative Medicine Winston-Salem, NC, USA.
authors.forename: Glicerio
authors.initials: G
authors.lastname: Ignacio
authors.affiliation: Regenerative Medicine, Wake Forest Institute for Regenerative Medicine Winston-Salem, NC, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Atala
authors.affiliation: Regenerative Medicine, Wake Forest Institute for Regenerative Medicine Winston-Salem, NC, USA.
authors.forename: Graça
authors.initials: G
authors.lastname: Almeida-Porada
keywords: fetal intervention; hemophilia; immune tolerance; in utero gene therapy; in utero transplantation; mesenchymal stromal cells; sheep model