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Over the last several years, DRI scientists have tried to "turn off" only the part of the immune system that attacks the transplanted islet cells -- allowing the rest of the immune system to continue to function normally.
Researchers focused their efforts on developing monoclonal antibodies, which selectively target specific cells of the immune system.
However, these agents are made of relatively large molecules, which researchers believe are likely to cause inflammation and other damage to the body, and to the cells themselves.
So the DRI’s Drug Discovery Program is focusing on designing and developing small molecule-based drugs that could eliminate these adverse reactions, and provide other benefits such as cost savings and easy patient administration.
The goal: to develop next-generation drugs that can block the key immune system pathways that lead to transplant rejection, such as pathway CD40-CD154.
The DRI has already shown that blocking this pathway in nonhuman primates has provided the most effective and longest lasting immunomodulatory intervention to date --effectively preventing rejection without toxicity to tissues, organs and the islets themselves.
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The small green, yellow and blue strands at the center of this 3-dimensional structure comprise the CD-154 co-stimulatory molecule which plays a central role in the rejection process.
The three longer strands are the antibody used to successfully block the signal in previous studies.
However, these antibodies caused side effects that could be eliminated if adequate small molecules can be identified.
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