COMPLETE SHORT-TERM CORRECTION OF CANINE HEMOPHILIA-A BY IN-VIVO GENE-THERAPY

Hemophilia A is a severe bleeding disorder caused by a deficiency in c lotting factor VIII (FVIII). A canine model that closely mimics the hu man disease was used to determine if an adenoviral vector expressing a human FVIII cDNA could be used to correct the hemophilia A phenotype. Within 48 hours after peripheral vein administration of the vector to FVIII-deficient dogs, the hemophilic phenotype was corrected, based o n determination of the activated cloning time, the activated partial t hromboplastin time, and the cuticle bleeding time, Direct measurement of human FVIII in the dog plasma showed FVIII expression at amounts we ll above the human therapeutic level, FVIII expression in treated dogs was short-term, lasting 1 to 2 weeks, due to the development of a hum an FVIII-specific inhibitor antibody response. These data provide the first demonstration of in vivo gene therapy of hemophilia A. (C) 1996 by The American Society of Hematology.