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The Inaugural MTI Humanitarian Award Celebration Honoring Alonzo Mourning

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Our Research - Liver & Gastrointestinal Transplantation


PROJECT 2: A New Family of Drugs to Prevent and Treat Rejection

PROJECT SUMMARY:

What is an aptamer?

Aptamers are very small molecules that we can synthesize in the lab.  We use aptamers, as carriers to transport a specific medication or agent to specific cells.  When we create an aptamer, we can design it in a way that it can bind to a specific cell with great specificity.  The aptamer will bind to only the cells we want and not to anything else.  At the same time we can create the aptamer to bind also to a specific medication or substance.  Using this method we can transport the medication to specific cells.  This method is currently used extensively in cancer patients, where with the use of aptamers we can direct chemotherapy agents directly to the cancer cells and spare the rest of the organs from the toxicity of the treatment (smart bomb concept).

What is rejection?

During a rejection episode in transplant patients, blood cells of the patient (lymhocytes B and T) attack the transplanted organ (liver or kidney) and destroy it.  This process is called a rejection. This is a normal defense of our body. It happens because the lymphocytes perceive the transplanted organ as foreign and want to destroy it.  Once the lymphocytes recognize the organ as foreign, they go through a process of activation and destroy it.

GOAL:

The goal of this project is to develop a clinically feasible strategy to eliminate activated B and T lymphocytes during episodes of rejection.

The approach is to use a carrier that can transport cytotoxic agents directly to the activated lymphocytes and destroy them.  This carrier is created in the lab and is called an aptamer.  We create a specific aptamer that can attach only to activated lymphocytes.

Then we attach to this aptamer a substance than can destroy these lymphocytes.  By injecting the aptamer carrying the killer substance in the patient it binds to the lymphocytes, destroys them and stops the process of rejection.

We plan to test this experimental approach to an animal model: Heart transplant and skin grafts in mice.  We prefer to use mice as they are the standard model to study immunology processes.  Additionally our lab has extensive experience in microsurgery procedures in this model.