Human anti-ADAMTS13 antibodies cloned from patients with acquired thrombotic thromobocytopenia purpura (TTP) for use in targeted therapies, and generation of animal models that recapitulate pathologic features of TPP.

Thrombotic thrombocytopenic purpura (TTP) is a rare but life-threatening blood disorder where blood clots form throughout the body to block the flow of oxygen-rich blood to major organs.

Acquired TTP is caused by the generation of autoantibodies to the ADAMTS13 metalloprotease enzyme to block its activity and cause inappropriate platelet clotting. First-line treatment involves plasmapheresis to lower autoantibody levels and replenish ADAMTS13 through transfusion of donor plasma. However, treatment is nonspecific, expensive, and not always effective. Additionally, the development of therapies has been limited by the lack of animal models specific to the human autoantibodies.

Dr. Donald Siegel and colleagues have cloned and sequenced human monoclonal ADAMTS13 autoantibodies from patients with acquired TTP. They have identified the specific sequences that block ADAMTS13 function to cause TTP pathogenesis. Using these recombinant human ADAMTS13 autoantibody sequences, a novel TTP murine model has been generated that recapitulates key pathologic features, and new therapeutics, such as anti-idiotypic antibodies, are currently being developed for the targeted TTP treatment, which improves specificity over current treatment methods.

• Provides an alternative improved, targeted and cheaper treatment for acquired TTP
• Improves animal models of TTP for more accurate testing of human therapeutic agents

• Development of more effective, targeted therapies for TTP, such as anti-idiotypic agents
• Generation of improved animal models of TTP that permits testing of therapeutics targeting human antibody/ADAMTS13 interaction