[Antithrombotic recombinant antibodies].
Coronary syndromes, stroke and other ischaemic arterial diseases are the leading cause of death in the world and will probably remain it at least until 2020. Cardiovascular diseases kill 17 million people each year with an expected increase to 20 million in 2020 and 24 million in 2030. The global impact of recurrence and death during the 6 months following an acute coronary syndrome remains at 8-15% in the present state of medical practice. Acute ischaemic syndromes have a common aetiology that is the formation of a platelet-rich clot at the site of severe coronary stenosis and of eroded atherosclerotic plaques. Therapy consists of medical treatments associating thrombolysis, antiplatelet drugs, and the re-opening of the coronary artery by angioplasty. But these treatments do not prevent morbidity and mortality reaching 15% at 6 months. Finally the treatment of stroke is very limited. There is thus a real clinical need to improve existing treatments and to discover new molecules. Platelet activation is a critical step in ischaemic cardiovascular diseases. This is the reason why antiplatelet drugs are most often prescribed in these cases. Currently, only one recombinant antithrombotic antibody is used in therapy. This is a chimeric Fab, c7E3 or abciximab, which inhibits the final phase of platelet aggregation. Abciximab is prescribed in acute coronary syndromes treated by angioplasty. However, treatment by abciximab can induce severe complications, principally, hemorrages and thrombopenia. Other platelet receptors involved in the earlier steps of platelet activation, such as the phases of contact with and of activation by the subendothelium matrix, have been identified as potential targets for the development of antithrombotic antibodies and are described in this revue.
Muzard
Julien
J
Inserm, U698, Hôpital Bichat, 46, rue Henri Huchard, Paris, France.
Loyau
Stéphane
S
Ajzenberg
Nadine
N
Billiald
Philippe
P
Jandrot-Perrus
Martine
M
D000906:Antibodies / Q000737:chemistry*; D000991:Antithrombins / Q000138:chemical synthesis* / Q000627:therapeutic use; D006801:Humans; D008958:Models, Molecular; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000627:therapeutic use; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000138:chemical synthesis; D014841:von Willebrand Factor / Q000276:immunology
D000906:Antibodies; D000991:Antithrombins; D010975:Platelet Aggregation Inhibitors; D011994:Recombinant Proteins; D014841:von Willebrand Factor