Technology Overview:
Roughly 12 million patients are exposed to heparin annually and up to 1% of these patients will develop heparin-induced thrombocytopenia/thrombosis (HIT), a life-threatening complication where patients make antibodies that bind to the heparin/PF4 complex, resulting in thrombosis and thrombocytopenia.
The Greene lab has identified and compared two antibodies respectively named KKO and RTO. KKO recognizes PF4 and stabilizes the complex with heparin, a critical initiating step in the pathogenesis of HIT. Conversely, RTO binds to an epitope that overlaps with KKO on the surface of PF4, preventing PF4 tetramerization, a critical step for the pathogenesis of HIT. This knowledge of KKO and RTO will support the development of an antibody assay to diagnose and/or monitor the progression of HIT but also the development of non-anticoagulant treatment.
Advantages:
- Knowledge of the first crystal structure of PF4 in a complex with Fabs
- Provides novel target epitope for diagnosing and the development of non-anticoagulant therapeutics for HIT
- Potential to decrease misdiagnoses, decrease rates of complications, and decrease mortality
State of Development:
- Solved crystal structure of PF4 in complex with antibodies
- In vivo data showing RTO prevent HIT induced by KKO
Case ID:
14-7144-tpNCS
Web Published:
1/23/2020
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