(Circulation. 1995;92:2373-2380.)
© 1995 American Heart Association, Inc.
Articles |
Blockade of Platelet GPIIb/IIIa Receptors as an Antithrombotic Strategy
From the Department of Medicine, Mount Sinai School of Medicine, New York, NY.
Correspondence to Dr Barry S. Coller, Department of Medicine, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, New York, NY 10029.
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Introduction |
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Moving from bench to bedside in the development of the monoclonal antibody 7E3, directed against the platelet GPIIb/IIIa receptor, from a basic science laboratory reagent to an antithrombotic drug was a long, incremental process. From the beginning, we hoped that this powerful new agent would allow us to define better the biochemistry of the GPIIb/IIIa receptor and its role in platelet physiology and pathology, and we dreamed that we might be able to use it to improve the therapy of patients with vascular disease.
I first review the evolution of our understanding of platelet
physiology since the 1960s and why the platelet GPIIb/IIIa receptor
appeared to be a logical target for antithrombotic therapy. I then
describe our studies with 7E3 to block the receptor in experimental
animal models of thrombosis. The results of these studies encouraged us
to try to develop 7E3 as a human therapeutic agent. The development was
a monumental effort conducted by hundreds of people working for nearly
a decade and culminated in the approval by the Food and Drug
Administration of c7E3 Fab (abciximab [ReoPro]) in December 1994 as
conjunctive therapy for use in patients undergoing high-risk
coronary artery angioplasty and atherectomy. A detailed
description of the developmental process is beyond the scope of this
essay, so it is only briefly described. My experience in moving back
and forth from the academic medical center research bench to the world
of drug development has allowed me to reflect on the processes
involved, and at the end of
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