Turning off inflammation, rebooting the immune system
One of the Alberta scientists working on translational research is AHFMR Scholar Dr. Paul Beck at the University of Calgary. He is a clinician-scientist. In other words, he is a physician—in his case a gastroenterologist—who also heads up a formal research program. "Clinician-scientists have a unique view on disease, how it comes on, and its interactions with drugs. We are on the front lines when it comes to seeing patients, and we know enough basic science to say, 'It might be this.' Our observations can be particularly relevant."
"I believe that looking at cell death may give us clues to IBD," says Dr. Beck. "If we could figure out the switch, we could design a drug to target it." The hypothesis is that in IBD there is no switch to turn off the inflammation. Instead, T cells (white blood cells whose specialty is to kill off any infection by means of inflammation) continue to respond and make the inflammation steadily worse. In the course of his investigation Dr. Beck has found two molecules that are responsible for stopping the inflammatory response by killing T cells.
Looking ahead, Dr. Beck is particularly excited by the potential of stem-cell transplants in the treatment of IBD. Worldwide to date, about 100 people with Crohn's disease have been treated with stem-cell transplants. Crohn's sufferers are genetically predisposed to the disease, which is first triggered when they come into contact with a particular environmental stimulus. The immune system responds, resulting in symptoms that blight the lives of sufferers. Transplantation "reboots" the immune system, restoring it to the state it was in before the onset of the disease.
The procedure involves three steps: (1) harvesting stem cells from the patient's own bone marrow (these are the body's "master cells", which can be directed to grow into cells of any other type); (2) killing off the patient's remaining stem cells, to knock out the entire immune system; and (3) re-introducing the previously harvested stem cells into the patient's bone marrow, where they give rise to a new generation of immune cells that function normally. Because all steps involve the patient's own cells, there is virtually no risk of rejection.
"The flaw in this treatment is that you are giving patients back their same immune system with the defective genes," says Dr. Beck, "so they are still susceptible to developing Crohn's. The extension would be to do gene therapy on the stem cells themselves to correct the defects before you give the stem cells back to the patients. We don't have the technology to do this right now, but I think it's not far off."