Recently, researchers investigating inflammatory bowel disease (IBD) at The Children’s Hospital of Philadelphia led an international collaboration of researchers to discover multiple gene variants responsible for developing early-onset and adult-onset IBD. And Robert Baldassano, MD, director of the Hospital’s Center for Pediatric IBD, says this discovery provides significant insight into the pathogenic mechanism mediating early-onset IBD.
Figuring out how IBD works, what causes it and, perhaps most crucially to current patients, how to better treat it, has proven to be a monumental research project. And as physicians’ understanding of the genetic underpinnings of IBD improves, a more personalized approach to treatment comes closer to reality. Once the underlying genetics are understood, Baldassano says, treatment could be tailored to a patient’s particular variant of IBD, increasing effectiveness and decreasing unnecessary side effects.
A genetic puzzle
But as CHOP researchers learn more about genes involved in IBD, they are also beginning to see that the disease is even more complex than first understood. Not only is the sheer volume of relevant gene variants high, it appears that some interrelate with other conditions.
Researchers at CHOP’s Center for Applied Genomics (CAG) published a study showing four genes are involved in both Crohn’s disease and type 1 diabetes, but with opposite effects, making Crohn’s less likely but type 1 diabetes more so.
“This finding shows the genetic architecture of these diseases is more complex than previously thought,” says study leader Hakon Hakonarson, MD, PhD, director of CAG at CHOP. “We knew that multiple genes that interact with each other and with environmental factors are needed to bring on these complex diseases, and we are still detecting these genes and uncovering those interactions. But we now see that some genes influence more than one disease, and sometimes in the opposite direction.”
While the research has not immediately translated into new treatments, discoveries from genomics and IBD researchers at CHOP are garnering significant attention in the medical field, illustrating their importance in laying a foundation for improved care in the future.
Two studies funded in part by the Stein-Bellet Foundation were presented in October 2011 at the 12th Annual International Congress of Human Genetics. One uncovered a genetic variant that promotes inflammation in Crohn’s disease. As more of the mechanisms of the disease are understood, more potential treatment avenues open up.
David Piccoli, MD, chief of the Division of Gastroenterology, Hepatology and Nutrition at CHOP, which houses the IBD Center, says that a project that combines research and patient care will have a direct impact on children being treated for IBD in the near future. This national initiative, led at CHOP by Andrew Grossman, MD, tests an approach to improve quality of care by providing clinicians with data-driven reviews of patients’ treatment prior to their appointments, pointing out measurements that vary from best practices so the treating physician can consider whether the discrepancy is thoughtful and beneficial or should be adjusted.
“The best care is done by thoughtfully applying what everyone has in a way that’s better,” Piccoli says. “If you can improve quality of care, you may cut costs, cut suffering, improve productivity, and change lives. In the next three years, that’s the single thing that will have the most effect on IBD patients.”