Current Research, Recent Success, and Future Developments

Dr. Michael Camilleri's interest is in the field of clinical enteric neuroscience research. He is director of Mayo's Enteric Neuroscience Program. His research focuses on increasing understanding of three main areas of digestive research:

• The role of particular nerves in controlling the way the stomach and intestine work.
• The influence of genetic differences on individual response to medications that work by affecting the nerves that control the digestive system.
• The stomach's role in determining the volume of food it takes for us to recognize the feeling of fullness and decide to stop eating.

How the Studies can Decrease the Burden of Human Disease

More than 35 million people in the U.S. are affected by disorders of gastrointestinal (GI) function. Symptoms from these conditions, such as constipation, diarrhea, and cramping, are the second leading cause for absenteeism in the workplace.

The three areas of Dr. Camilleri's research affect patient care by:

1. Studying how the adrenergic nervous system controls the GI system and learning ways to manipulate specific mechanisms that can relieve patient symptoms such as diarrhea, constipation, pain, and indigestion after eating.
2. Participating in the field of pharmacogenomics to contribute to the development of drugs designed to provide the greatest relief of symptoms with the least risk according to an individual's genetic makeup. Studies have already demonstrated that individual genetic differences influence the effectiveness of medication to control the rapid movement of the colon's content that results in diarrhea.
3. Developing novel approaches to address the epidemic of obesity. Dr. Camilleri's studies have shown that appetite-suppressing drugs have a direct effect on the stomach. His current studies expand on this knowledge to focus on developing new medications and devices that regulate food intake by manipulating the way the stomach accepts food.

Recent Success Helps Patients with Irritable Bowel Syndrome

In the early 1990s, Dr. Camilleri conducted studies to explore how particular nerve receptors control the colon's muscles and nerves. The nerve receptors respond to chemical messengers, called 5-HT. Dr. Camilleri's research demonstrated that medications that modify two of the 22 subclasses of 5-HT can be regulated to change the contractions of the colon after feeding. The contractions determine whether the patient will experience urgency and diarrhea, or have no response, resulting in constipation.

After lengthy multi-center clinical trials, the Food and Drug Administration (FDA) approved two new medications:

• Alosetron (Lotronex®), which can decrease motor function in women with severe diarrhea-predominant irritable bowel syndrome.
• Tegaserod (Zelnorm®), which can increase motor function to facilitate the movement of food, gas, and stool through the bowels, is primarily used to treat women who have irritable bowel system with predominant constipation.

"It is satisfying to know that my laboratory played a significant role in the acquisition of knowledge necessary to develop these drugs," says Dr. Camilleri. "This is a fine example of Mayo's ability to translate science into treatments that improve patient care."

Virtual Reality—Examination Without the Tubes

Dr. Camilleri also has developed a unique technique in collaboration with colleagues in Biomedical Imaging and Nuclear Medicine. The test is painless and takes 45 minutes. It replaces a two to three-hour test that involved placing a large tube through the nose or mouth into the stomach.

The technique allows visualization of the stomach wall in order to measure its volume and motor responses—functions that are important determinants of how much a person can eat without feeling uncomfortable and, therefore, relevant to conditions such as obesity, anorexia nervosa, and dyspepsia (indigestion after eating).

Here's how the test works:

1. A radioactive substance that concentrates in the lining of the stomach is injected into the patient's veins.
2. An external camera rotates around the abdomen, picks up the radioactive signal from the stomach and measures the surface area of "virtual" horizontal slices through the stomach.
3. A computer program reconstructs the stomach in three dimensions and automatically measures its volume during fasting, after feeding, or after a medication is given.

The test makes use of a computer program, called ANALYZE, developed by scientists in Mayo's Department of Physiology and Biophysics. The program allows surgeons, physicians, and basic scientists to explore virtually many of the body's systems.

"Mayo's support of the 3D program, and of our excellent facilities at the CTSA Clinical Research Unit (CRU) makes our work possible," says Dr. Camilleri. "We use the test both in clinical practice to diagnose conditions that result from malfunction of the stomach, and in research to increase our knowledge of how the stomach works. Our goal is to use the knowledge to develop more effective medications or devices to help combat the obesity epidemic."