The Kenneth Rainin Foundation announced that Sanford-Burnham’s Dr. Fred Levine and Dr. Hudson Freeze will receive a 2011 Innovator Award for Inflammatory Bowel Disease (IBD) Research. The team will receive a $100,000, one-year grant for their idea to develop new IBD treatments by targeting a protein called HNF-4a.
HNF-4a is a nuclear receptor, meaning that it directly binds DNA and turns genes on or off in response to outside signals. HNF4a is found throughout the intestine, where it helps maintain structural integrity of the intestinal lining. Previous studies suggest that HNF4a might play a role in IBD. In a mouse model of IBD, lack of HNF4a increased disease severity. HNF4a levels are also low in intestinal biopsy samples from IBD patients. Given this information, it makes sense that enhancing HNF4a function might have the opposite effect, diminishing the disease. However, there hasn’t been a practical way to do that—until now.
Using the resources of the Conrad Prebys Center for Chemical Genomics, Dr. Levine’s lab recently discovered new compounds (prototype drugs) that activate HNF4a. Then, working with Dr. Freeze’s lab, they showed in cell culture models that those drugs completely reverse the effects of the inflammatory protein TNFa on cell leakiness, a major characteristic of IBD. In fact, antibodies against TNFa are the mainstay of current therapies for severe IBD.
“With this new award, we’ll take our findings in cell culture models and apply them to animal models of IBD. Our goal is to use these compounds that boost HNF4a activity to ameliorate IBD,” says Dr. Levine.
Approximately five million people worldwide suffer from some form of IBD, a group of inflammatory conditions that includes Crohn’s Disease and ulcerative colitis. While symptoms can be managed using anti-inflammatory steroids, removal of the colon is currently the only cure for IBD.
The Innovator Awards Program for IBD Research specifically funds projects that show strong evidence of collaboration, scientific merit, and a high potential for success. The Kenneth Rainin Foundation especially looks to fund projects that, due to their innovative nature, may not be eligible for funding from the National Institutes of Health (NIH) or other more traditional sources.
In a statement released by the foundation, Jen Rainin, the foundation’s president, says, “By supporting these outstanding projects, we are steadily making headway towards accomplishing the Foundation’s mission of no one suffering from IBD. My late father, Kenneth Rainin, would be elated by the progress that is being made.”