Inhibition of Hyperacute Rejection in Pulmonary Xenograft

Summary

One of the several problems with organ transplantation is the actual procurement of needed organs. The number of patients requiring transplants far exceeds the number of available organs. Thus, tissues and organs from different species (xenografts) may offer help to many more potential organ donors, and consequently may help the organ shortage. However, many obstacles still remain with xenografts, with the major challenge being tissue/organ rejection. The need to reduce this rejection and the injury it can inflict upon the transplanted tissue/organ therefore remains high. Vanderbilt researchers have patented a technology that helps to prevent the rejection of transplanted tissues/organs and the injury that occurs to these tissues. This technology inhibits specific pathways that regulate platelet adhesion and aggregation, which have been linked to the rejection of transplanted tissues/organs.

Description

Inappropriate platelet aggregation causes numerous complications for many cardiac and transplant patients. Most heart attacks are caused by a blood clot blocking a coronary artery and are treated early using thrombolytic agents. These clot-dissolving drugs are often combined with antiplatelet agents such as aspirin and ReoPro or anticoagulants such as heparin or Coumadin. By reducing the tendency of blood platelets to clump and initiate clot formation, antiplatelet drugs lessen the possibility that the artery will reclose and improve chances of survival for cardiac patients. In addition to cardiac patients, antiplatelet agents are often given to tissue/organ transplant patients. Donor rejection in transplant patients remains extremely high. One prominent cause of delayed tissue/organ rejection is due to micro vascular thrombosis. Several studies have suggested that antiplatelet agents may help increase tissue/organ survival.

Normally platelet aggregation occurs when specific proteins that belong in tissues are released and detected into the bloodstream. Once these proteins are detected, the clotting cascade is signaled, and numerous proteins and enzymes begin the formation of a clot. Several studies have shown that platelet membrane glycoproteins (GPs) are involved in both platelet aggregation and the formation of platelet thrombi, and thus are the targets for antiplatelet therapies.

Vanderbilt researchers have discovered inhibitors in the platelet receptors for thrombin and fibrinogen. By blocking both of these receptors, complement activation is inhibited, and platelet aggregation can be prevented. Complement activation is the biochemical cascade of the immune system which clears pathogens and is a prevalent mediator of many types of tissue injury. This technology is novel and effective because it blocks both platelet receptors rather than only blocking one, which is the current method used to modulate the complement system. Therefore, this technology may have very broad applications, as it may help with resulting tissue injury acquired from surgery or tissue transplantation.

Value Proposition

This patent may cover any application where the intent is to protect from injury that may be mediated by the complement activation pathway.

Current Competitive Products

Currently GPIIB3A blockers are available, which will only block one platelet receptor. No GP1B blockers are available.

Intellectual Property Status

U.S. patent # 6,538,028 was filed May 23, 2000 and issued March 25, 2003

Inventors: 
Richard PiersonTodd GiorgioGeorge ZornAgnes AzimzadehSimon Robson
Licensing manager: 
Janis Elsner

Featured Video

Vanderbilt Patent Activity

View Vanderbilt University Patents

CTTC on Twitter