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ΓÇ£Platelet silencingΓÇØ using antibody to Fc╬│RIIa

技术优势

Platelet accumulation at sites of vascular injury, even if unintentionally introduced during surgical procedures, is a life-threatening event, for which there are currently no highly-specific treatments. Current drugs dampen platelets or block their ability to form a thrombus, but since they block platelet activation induced by numerous agonists, also carry a risk of bleeding and hemorrhage. We expect that an antibody specific for Fc╬│RIIa will prevent local injury induced thrombosis without the associated risks of bleeding seen with other compounds.

技术应用

This technology is particularly applicable to the surgical market and could provide a superior means of preventing re-stenosis following implantation of surgical stents. Injection of Fc╬│RIIa antibodies in mice temporarily silences platelets and their ability to clot or occlude a vessel after injury. Control of clot formation at the site of injury is necessary in surgical procedures involving large vessels. Currently, stents and drug-eluting stents help to keep vessels open after surgery.However these stents can increase the likelihood of thrombosis as platelets are exposed to extracellular matrix proteins. Because this antibody inhibits thrombus formation in response to vascular injury, without an increase in bleeding, it may prove superior to currently available methods for preventing re-stenosis and other complications following coronary angioplasty.

详细技术说明

Platelets form clots in response to various activation signals and duringvessel injury. This invention describes the use of an antibody directedagainst Fc╬│RIIa, a newly discovered amplifier of platelet activationmediated by the platelet adhesion and signaling receptor, ╬▒IIb╬▓3.We demonstrate with various experimental systems both in vitro and in mice that Fc╬│RIIa (CD32a) functions as an amplifier of platelet activation mediated by the platelet integrin ╬▒IIb╬▓3, also known as glycoprotein (GP) IIb-IIIa. GPIIb-IIIa is required to support stable platelet-platelet interactions, and is thus critical to the formation of a stable clot in arteries. This antibody against Fc╬│RIIa does not clear platelets from the circulation, but instead disrupts the amplification of platelet activation that results from ╬▒IIb╬▓3 activation. We have demonstrated that an antibody against Fc╬│RIIa inhibits platelet activation and thrombus formation in response to various platelet agonists and prothrombotic surfaces (e.g. collagen, fibrinogen) and inhibits thrombus formation in vitro and that expression of Fc╬│RIIa dramatically enhances thrombus formation in vivo in a mouse model of vascular injury. Anti-Fc╬│RIIa therefore has the ability to dampen platelet activation and inhibit thrombus formation, and may be a therapeutically useful tool in clinical conditions in which there is a risk of thrombosis (sepsis, HIT, atherosclerosis).

*Abstract

Platelets form clots in response to various activation signals and duringvessel injury. This invention describes the use of an antibody directedagainst Fc╬│RIIa, a newly discovered amplifier of platelet activationmediated by the platelet adhesion and signaling receptor, ╬▒IIb╬▓3.

*Principal Investigation

Name: Peter Newman

Department:

国家/地区

美国