A quantitative measure of the efficacy of factor VIII in hemophilia A mice.
We developed a quantitative method to study the efficacy of intravenously delivered human factor VIII in hemophilia A mice. Mortality was assessed after tail transection under conditions in which there were no survivors in untreated hemophilia A mice. Blood loss was significantly greater in untreated hemophilia A mice compared to normal C57BL/6 mice, and in hemophilia A non-survivors that were treated with sub-therapeutic doses of factor VIII. The up-and-down method for small samples yielded an estimated dose of factor VIII producing survival in 50% of the mice (ED(50)) of 58 units/kg (95% confidence interval: 42.4-78.5 units/kg). This method should be useful in the evaluation and comparison of novel factor VIII products delivered either parenterally or in a gene therapy setting.
Parker
Ernest T
ET
1639 Pierce Drive, Room 1003 Woodruff Memorial Building, Emory University, Atlanta, GA 30322, USA.
Lollar
Pete
P
D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005169:Factor VIII / Q000008:administration & dosage*; D005260:Female; D006467:Hemophilia A / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011994:Recombinant Proteins / Q000008:administration & dosage
D011994:Recombinant Proteins; D005169:Factor VIII