New Studies, New Hope

GI technicain Michelle Macias(left) and Brigid Boland, MD, prepare to take colonic biopsies during a colonoscopy at Thornton Pavillion.GI technicain Michelle Macias(left) and Brigid Boland, MD, prepare to take colonic biopsies during a colonoscopy at Thornton Pavillion.

GI technicain Michelle Macias(left) and Brigid Boland, MD, prepare to take colonic biopsies during a colonoscopy at Thornton Pavilion.

CTRI "LaunchingPad" Spawns IBD Research Project and New Hope for Patients

August 19, 2013 – William Sandborn, MD, has always been interested in exploring the connection between rheumatoid arthritis and inflammatory bowel disease (IBD). Inflamed and painful tissues are common to both diseases. He wanted to see if medications effective in treating rheumatoid arthritis might help patients with IBD. To Sandborn, Chief of the Division of Gastroenterology and Professor of Medicine at UC San Diego School of Medicine, IBD is "rheumatoid arthritis of the gut."

William Sandborn,MD

William Sandborn,MD, Chief of the Division of Gastroenterology and Professor of Medicine at UC San Diego School of Medicine

Exploring the link became a reality when Gary S. Firestein, MD, and David Boyle approached Sandborn to collaborate. Firestein is the Director of the Clinical and Translational Research Institute (CTRI), Dean and Associate Vice Chancellor of Translational Medicine at UC San Diego School of Medicine and Boyle is Professor of Medicine and co-director for the Translational Research Technology Division (TRT) in CTRI.

The IBD research collaboration is the first for CTRI's "LaunchingPad," which is a new program that guides clinical investigators interested in planning biomarker-based clinical studies. Biomarkers are molecules that can be measured in patients and can assess disease activity. Through TRT, the institute provides laboratory, clinical, and bio-repository collaboration and services.

"Through this collaboration, we kick off the LaunchingPad, which is one of the ways we continue to make strides translating outstanding science into improved health care," said Firestein. "I'm delighted to begin with this project."

The genesis for the combined effort was the rheumatoid arthritis investigations and discoveries by Firestein and Boyle that synovial biopsies from arthroscopic examinations of joints could provide crucial information on the mechanism of action for various drugs. The research led to a number of insights about what causes rheumatoid arthritis and how drugs thought to be effective really work, said Sandborn, who had been at the Mayo Clinic in Minnesota before joining UC San Diego in 2011. "All of the experience and learning that they had acquired over the years in rheumatoid arthritis, in many respects, could be transferred over and applied to our research," said Sandborn, the principal investigator on the IBD project and an internationally esteemed IBD clinician and researcher.

The IBD team's quest is to understand the pathogenesis of the disease, as well as the mechanism of action of the drugs used for treatment, said Boyle. Looking at biomarkers before, during and after therapy could lead to new discoveries in the diagnosis and treatment of IBD, which includes ulcerative colitis and Crohn's disease.

"I thought what they were doing was very interesting and that we could apply the same techniques to research in our area," Sandborn said. His IBD project team, just like the rheumatoid arthritis team, began with an extensive series of studies to validate the methods before testing any drug.

The IBD team defined the size and number of biopsies needed to be able to see particular biomarkers in the inflamed colon, and the regions from which to take the biopsies. "You want to get that information really well characterized so that when you collect the samples you end up with something that's reproducible over time and that shows accurate results," said Sandborn, who designs and implements clinical trials. "We recruited about 40 patients with ulcerative colitis and Crohn's disease, some in remission and some with flare-ups, and also recruited healthy patients undergoing colonoscopy screening for colon cancer."

The preliminary data suggest that the methods will work as well for IBD as they do for RA. "We're looking at a variety of inflammatory signaling pathways," Sandborn said, noting that not all drugs that work for rheumatoid arthritis work for IBD, and vice versa, but a number do. "So that will be interesting in both directions."

Brigid Boland, MD, prepares to take colonic biopsies. She is on the IBD research project team.

Brigid Boland, MD, prepares to take colonic biopsies. She is on the IBD research project team.

CTRI funds the project, in part. Going forward, support will come from a combination of federal funding through NIH and private industry along with potential for co-funding from the CTRI. Forming the collaboration, securing protocol approvals, and recruiting subjects took about 18 months. However, the team is now ready to begin using the technology to test new therapies for IBD. The CTRI group is also interested in "launching" programs in other diseases.

Sandborn praised the collaboration enabled by LaunchingPad. "I hope this is the first step in a rich collaboration in the years to come with CTRI," said Sandborn. "It's a credit to Dr. Firestein and Mr. Boyle that they've created this program in CTRI."

The endgame for the team is accelerating the delivery of treatment and improving the lives of patients. "In translational medicine, there is clinical work and research," Sandborn said. "You see patients in clinic and you're constantly reminded of the problems they face and that someone needs to help them solve these problems."

What will potentially come out of the studies will move physicians further down the path of personalized medicine. "This type of research will allow us to magnify the differences in patients and why they might respond to one medication and not another," he said.

Every team member and every group plays a critical role in the ever widening scope in collaborative investigations. "It takes a village to do research like this," Sandborn said.

Team: William Sandborn, MD, Brigid Boland, MD, John Chang, MD, and Lars Eckmann, MD, PhD

The CTRI invites researchers to explore whether the LaunchingPad methodology might be beneficial to their research. If you would like to learn more about the program, please contact us [TRT] or submit a service form for a TRT consultation [CTRI Service Request Form ]

Written by Patti Wieser

 

 

 



About UC San Diego Altman Clinical and Translational Research Institute:

UC San Diego Altman Clinical and Translational Research Institute (ACTRI) is part of a national Clinical and Translational Science Award consortium, led by the National Institutes of Health National Center for Advancing Translational Science. Established in 2010, ACTRI provides infrastructure and support for basic, translational and clinical research throughout the San Diego region to bring discoveries from the laboratory to the bedside, and facilitates training and education of the next generation of researchers. ACTRI carries out its activities in collaboration with institutional and corporate partners and currently has more than 1,400 members.

actri.ucsd.edu