TY - JOUR
T1 - Hemophilia A
T2 - An ideal disease to correct in utero
AU - Porada, Christopher D.
AU - Rodman, Christopher
AU - Ignacio, Glicerio
AU - Atala, Anthony
AU - Almeida-Porada, Graça
N1 - Publisher Copyright:
© 2014 Porada, Rodman, Ignacio, Atala and Almeida-Porada.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - Fetal intervention
KW - Hemophilia
KW - Immune tolerance
KW - In utero gene therapy
KW - In utero transplantation
KW - Mesenchymal stromal cells
KW - Sheep model
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U2 - 10.3389/fphar.2014.00276
DO - 10.3389/fphar.2014.00276
M3 - Review article
AN - SCOPUS:84921761152
VL - 5
JO - Frontiers in Pharmacology
JF - Frontiers in Pharmacology
SN - 1663-9812
IS - DEC
M1 - 276
ER -