CCE Gastrointestinal Disorders: Mayo Clinic

Mayo Clinic
Rochester, Minnesota

When it comes to research into and treatment of gastrointestinal disorders, the Mayo Clinic believes there is strength in numbers.

"When you have 75 faculty and a strong referral base, you have the luxury of allowing people to differentiate into their clinical niches and areas of technical proficiency," says Gregory Gores, MD, professor of medicine and physiology and chair of the Mayo Clinic Division of Gastroenterology and Hepatology.

Along with the division's size comes experience. Division members perform close to 50,000 procedures each year. Moreover, a culture that emphasizes teamwork and cross-departmental collaboration ensures that knowledge is readily shared among researchers and clinicians.

Much of the basic and clinical research on disorders of the GI tract takes place in the Enteric Neuroscience Program (ENSP). ENSP currently includes 23 staff members in nine laboratories researching diseases ranging from the fairly common, such as functional dyspepsia, to rarer conditions such as chronic intestinal pseudo-obstruction.

Motility Disorders

Gianrico Farrugia, MD, professor of medicine and physiology and ENSP director, focuses on the cellular and molecular activities underlying motility disorders. Farrugia has found that interstitial cells of Cajal, which function as a "pacemaker" of the guts, are often being lost in patients experiencing severe chronic constipation. "We are very interested in why these cells are being lost, and what we can do to make them come back," he says.

Farrugia's lab has also found that interstitial cells of Cajal are decreased in patients experiencing gastroparesis. Using a mouse model, his lab team has found that the enzyme hemoxygenase-1, which produces carbon monoxide, is down-regulated in patients with the disease. Farrugia was to present data from his studies at Digestive DiseaseWeek in June. "We'll be showing that if you give these mice very low doses of carbon monoxide, within three weeks you can reverse the cellular defect and restore gastric emptying back to normal," he says.

Integrating Research and Clinical Care

Farrugia says his work is an example of the integrative approach to research and clinical care at Mayo Clinic. "You take a clinical disease, work out the basic mechanism, and then start moving toward therapy. At some point we will hand off to colleagues, who will take the next step in healing, he says. Farrugia adds that enteroscience research collaborators are plentiful with 75 gastroenterologists on staff.

Several ENSP members share an interest in pharmogenomics, the study of why groups of people respond differently to different drugs. "Dr. Camilleri (Michael Camilleri, MD, professor of medicine and physiology) has published work showing that there are different polymorphisms that can predict the response to certain medications. And therefore you can get to the point where you can target therapy based on knowing what those polymorphisms are," Farrugia says.

The emphasis on collaboration, according to Gores, will be further strengthened with a five-year, $5-million grant Mayo expects to receive from the National Institutes of Health later this year. "That grant is built around facilitating collaborations between clinical investigators and those in discovery sciences," he explains.

Understanding Incontinence

Professor of Medicine Adil E. Bharucha MD, MBBS, draws on Mayo Clinic resources in epidemiology, gynecology, and radiology, in his efforts to understand the causes of, and develop treatments for, fecal incontinence, a common problem among women over age 50. Bharucha and fellow researchers surveyed Rochester-area women to ascertain incontinence's prevalence and effect on quality of life. The team also interviewed a sampling of respondents with and without incontinence, compared their medical and obstetrics records, and conducted MRI studies.

Bharucha has also been investigating the internal mechanisms of incontinence. Current theory, he says, is that the problem is caused by sphincter muscles damaged during childbirth. However, the incidence of sphincter muscle damage is much greater than that of stool leakage. Moreover, Bharucha says, many of his patients and research subjects experience tremendous urgency.

Bharucha and his colleagues found that in a subset of women with the symptom of urgency, the rectum was stiffer and more sensitive than those without the urgency. "So now we're trying to understand if this stiffness is reversible, and if it is, can we give patients medications to try and restore the reservoir?" he says.

A controlled study testing the effects of clonidine, a drug previously shown to be effective in reducing the perception of balloon distension and relaxing the rectum, is under way. Results from a pilot study are due to be presented at the 2009 Neurogastroenterology and Motility Joint International Meeting in August.

Cristina Calin, MD, a family practitioner in Grand Forks, North Dakota, refers two to three GI patients a year to Mayo Clinic. She says her patients receive "an excellent level of care" at and the clinic's staff is responsive to her requests for consultations and updates. "I'm very happy with their service and care, and will continue to send patients there," she says.