photo via Maggie Bartlett, NHGRI

The Genome's Path to a Cure for Crohn's

Bringing together the best and brightest, the Broad Institute marshals its shared experience to develop the next generation of safe and effective therapies for Crohn's disease.

Science has well established that genes play a chief role in the development and progression of certain diseases. But oftentimes there is little known about the specific genes that lead to a disease, creating a great many unanswered questions.

In 2010, Helmsley’s Crohn’s Disease Program provided a three-year grant to the Broad Institute of Harvard and MIT to systematically study the function of genes in regions associated with Crohn’s disease. Challenged to identify the biological context in which these genes act, the researchers set out to provide the necessary basis for the next steps of small molecule discovery and the development of early stage therapeutics.

The Broad Institute is a joint venture that provides preeminent scientists with cutting-edge technologies in genomics and related disciplines in order to understand human disease at the genetic level. The Institute unites over 150 faculty and 1,000 investigators from Harvard and MIT, comprising a multidisciplinary platform of expertise ranging from genome sequencing to therapeutic discovery and development of cures.

There is perhaps no other institution in the world that can assemble such a formidable team of scientists across so many disciplines to tackle the great challenge of solving these diseases.

Trustee Sandor Frankel

Screening genes associated with Crohn’s disease, these researchers identified new pathways by which inflammation in the gut is caused, aggravated or modified. To build upon the encouraging early discoveries, Helmsley renewed and expanded its Crohn’s funding for the Institute in 2013 to begin new work with three major aims: 1) continue studies of individual genes to determine how genetic differences between Crohn’s patients and healthy individuals contribute to the disease; 2) evaluate promising small molecules in disease-relevant studies and prioritize insights from genetics to help develop novel therapeutics; and 3) begin basic experimentation in animal models with Crohn’s disease to provide the data necessary to begin testing new therapies in humans. 

By comparing the genomes of patients with inflammatory bowel disease to those without, research has already been able to uncover several genetic factors that may influence whether an individual may develop IBD. Efforts to understand the functions of these genes have provided novel insights into the underlying biological causes of disease that would otherwise have remained undiscovered.

"This project has dramatically expanded our understanding about the nature of IBD and autoimmune disease,” said Dr. Eric Lander, president of the Broad Institute. “With the visionary support of the Helmsley Charitable Trust, the research team at the Broad Institute and Massachusetts General Hospital is revealing a comprehensive picture of the genes and circuits that cause Crohn’s disease. This remarkable progress lays the critical foundation for discovering new drugs that could help prevent and treat Crohn’s disease and related diseases."

The Institute’s combination of genetic expertise, small molecule screening libraries and high-throughput screening equipment uniquely allows scientists to continue testing new genes faster than possible at most other institutions. Dr. Ramnik Xavier, senior associate member of the Institute and chief of gastroenterology at Massachusetts General Hospital, explains: “Many of the research methods and state-of-the-art tools we use to study genetic variant discovery and gene function were developed right here at the Broad. The Institute brings together the collective wisdom of Harvard, MIT and the Harvard-affiliated hospitals, putting our research team in the unique position to interact with not only geneticists, but also superstars in every field of biomedicine.”

“Our support for the Broad Institute underscores the critical importance of bench science in laying the foundation for the translational advances that someday will bring about a cure for IBD and Crohn’s, which is the singular goal of our program,” said Helmsley trustee Sandor Frankel. “There is perhaps no other institution in the world that can assemble such a formidable team of scientists across so many disciplines to tackle the great challenge of solving these diseases.”