The hemophilias (A and B) are rare bleeding disorders toward which much scientific and medical effort has been devoted. In 1840, blood transfusion was used for the first time to stop post-operative bleeding in a hemophilia patient and in 1968 the first commercial coagulation factor concentrate became available. The cloning of the fVIII gene in 1984 facilitated the development of recombinant fVIII protein products that became commercially available in 1992. This was viewed as a dramatic therapeutic improvement due to the perceived safety advantage recombinant products have over plasma-derived products, which proved responsible for the infection of thousands of patients with hemophilia with human immunodeficiency virus and/or hepatitis C virus during the 1980's. Since the development of recombinant fVIII, progress in the treatment of hemophilia A has slowed. The current limitations to treatment are 1) access to fVIII-replacement products, 2) the cost of fVIII- replacement products, 3) the development of anti-fVIII immune responses that block treatment efficacy and 4) morbidity due to joint disease. Unless the worldwide fVIII supply increases and prices drop significantly, hemophilia A will remain an important heath burden to human society. Therefore, the search for improved therapeutics is warranted. One strategy for improving hemophilia A care is to develop improved recombinant- protein products, e.g. manufactured more efficiently or have increased hemostatic efficacy. The mission of Expression Therapeutics is to develop products that will improve the treatment of individuals with hemophilia A. Our technology is based on the identification of sequence elements within fVIII that can be modified to increase its'biosynthesis. The goal of the current study is to provide preclinical data necessary to get FDA approval to conduct a phase 1 human clinical trial using a high-expression fVIII-replacement product that can be manufactured more efficiently than traditional human recombinant fVIII products. These data will support the commercialization of a novel fVIII-replacement product that will improve the treatment of hemophilia A.

Public Health Relevance

Hemophilia A is a bleeding disorder caused by the insufficiency of a blood clotting factor, termed factor VIII (fVIII). Current treatment for hemophilia relies on infusion of plasma-derived or recombinant fVIII products to restore circulating fVIII activity. Currently, treatment is offered to less than one-third of all patients due to excessive product cost. Unless the worldwide fVIII supply increases and prices drop significantly, hemophilia A will remain an important heath burden to human society, and therefore, the search for improved therapeutics is warranted.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Small Business Technology Transfer (STTR) Grants - Phase II (R42)
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Special Emphasis Panel (ZRG1-VH-E (10))
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Pucie, Susan
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Expression Therapeutics
United States
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Spencer, H Trent; Denning, Gabriela; Gautney, Richard E et al. (2011) Lentiviral vector platform for production of bioengineered recombinant coagulation factor VIII. Mol Ther 19:302-9