The Role of Anti-Rejection Drugs in Re-Educating the Immune System
Background:
When a diabetes patient receives a transplant of insulin-producing cells, he or she must take powerful anti-rejection drugs, or immunosuppressants, for life. While the drugs are needed to prevent rejection of the transplanted cells, they present their own set of challenges. Immunosuppressants:
- Can cause harmful side effects and could even damage the transplanted cells
- Suppress the entire immune system, leaving the patient susceptible to viruses and infections
If anti-rejection drugs could be re-engineered, to address those two issues, we could increase the long-term viability of islet transplants and improve the quality of life of the transplant recipient.
Research Focus:
At the DRI, we’re engineering new drugs to overcome those challenges. Within our Drug Discovery Program, we’re implementing a two-pronged approach: modify the drugs themselves, then deliver them to a specific location where they can do their work efficiently and without causing unnecessary harm to the transplant recipient.
First, the location. We’ve identified critical signaling pathways that trigger the immune system to reject transplanted cells or tissues. By delivering anti-rejection drugs precisely to those locations, we can block the pathway and suppress the immune system signals – effectively preventing rejection.
Next, the drugs themselves. Until now, scientists have been using immunosuppressants called “monoclonal antibodies.” These molecules are relatively large in size and researchers believe because they’re so big, they cause inflammation and other damage to the body. So our Drug Discovery Program is focusing on designing and developing smaller molecule-based drugs that could eliminate these adverse reactions.
Leading to a Cure: How this Research Supports our Mission
By developing next-generation, small-molecule drugs that can block those key immune system communication pathways, we hope to induce transplant tolerance while at the same time minimizing the anti-rejection drug’s toxic effect on tissues, organs and the islets themselves.
Peter Buchwald, PhD., Director of the Drug Discovery Program, talks about his program's two areas of focus.
DRI researchers are developing small molecules to block key immune response pathways to prevent rejection.