A Study Digest
Inflammatory bowel disease (IBD), a disorder that affects more than 3 million Americans, is in fact several diseases, each with a different biology. This hypothesis has anchored decades of groundbreaking research led by Stephan Targan, MD, director of the F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute at Cedars-Sinai and the Feintech Family Chair in Inflammatory Bowel Disease.
The National Institutes of Health (NIH) recently awarded Targan’s research team the final installment in a series of prestigious grants that fueled a quarter century of discovery. This timeline traces the research from the seed of a great idea to tangible advancements that are improving the lives of people around the world.
Targan gathers an international group of investigators to study IBD from all vantage points. Wide variability in symptoms and response to treatments suggests many more forms of IBD than the two primary classifications: Crohn’s syndrome and ulcerative colitis. Higher risk among Ashkenazi Jews and the observation that the disease runs in families indicate a genetic component.
Targan’s group moves from UCLA to Cedars-Sinai. The NIH awards the first in a special category of grants that support a multidisciplinary approach. The team’s work targets two questions: 1) What is the nature of the genetic complexity of IBD? and 2) What immune system switch is flipped to turn a brief inflammatory response into a chronic one?
The investigators build on their discoveries of IBD-associated blood markers and genetic abnormalities to form a clearer picture of the different types of the disease. Based on these findings, they launch the signature Cedars-Sinai approach to IBD treatment.
The team discovers that a protein known as TNF plays a role in Crohn’s syndrome. Targan leads the first trial of a biologic — a therapy derived from a living organism — to target TNF. The researchers introduce noninvasive diagnostic tests and methods of predicting drug toxicity and optimal dosing.
Resurgent interest in the role of intestinal microbes, aka the microbiome, combined with advanced genetic analysis technology, leads to intense focus on how genes and the microbiome interact in IBD. A Cedars-Sinai priority on merging basic science with clinical practice lays the groundwork for the IBD translational medicine program (launched in 2007).
The IBD team embarks on a 15-year effort to define the contribution of a novel protein, TL1A, to IBD, ultimately showing that it is a master regulator of inflammation. This pivotal discovery will lead to efforts to develop a drug to counteract TL1A’s effects.
Through the manipulation of certain genes, improved animal models better reflect human IBD, leading to insights about complicated forms of the disease.
A transformational donation from the F. Widjaja Foundation names the institute, fostering the creation of unique programs. This and other generous gifts allow the luxury of taking chances with high-risk/high-reward, integrated science not possible with conventional funding.
Institute investigators are the first to define a role played by intestinal fungus in IBD, opening a novel area of study and potential treatments. The Cedars-Sinai IBD Drug Discovery and Development Unit is established to accelerate the speed at which scientific concepts can be applied to treat IBD by defining the genetic and biologic characteristics of patient populations most likely to respond to new therapeutics.
Stem cell research makes possible human intestinal models of IBD and new treatment opportunities.
To date, 20,000 individuals have participated in research at Cedars-Sinai to usher in an era of precision medicine for IBD. The institute continues to aim for improving care for patients, wherever they live.