Investigating Treatments for Inflammatory Bowel Disease

UH Inflammatory Bowel Disease Center advances clinical research and therapies to treat Crohn's disease and ulcerative colitis

UH Digestive Health Institute - Winter 2018 

Fabio Cominelli, MD, PhD

 Maneesh Dave, MD, MPH

 Jeffrey Katz, MD

A review led by Mahmoud Ghannoum, PhD, of the University Hospitals Cleveland Medical Center dermatology department, made headlines recently for its finding that certain fungi may play a key role in Crohn's disease and ulcerative colitis, collectively known as inflammatory bowel disease (IBD). The report, published in the Journal Digestive and Liver Disease, is not the only UH project aiming to improve treatments for IBD.

A team led by Fabio Cominelli, MD, PhD, Chief Scientific Officer and Division Chief of Gastroenterology and Liver Diseases, UH Cleveland Medical Center and Professor of Medicine, Case Western Reserve University School of Medicine, is using unique mouse models to study the gut microbiome and determine which bacteria may be responsible for IBD. These mouse models are among the best in the world at mimicking human Crohn’s disease; they allow us to understand the disease before its onset and test novel therapies before initiating expensive clinical trials.

Dr. Cominelli is spearheading a project to collect stool samples from families with multiple members diagnosed with IBD, as well as from healthy patients. He uses the samples to model the effects of both IBD and healthy gut bacteria in germ-free mice (mice reared in a sterile environment) to determine which bacteria are beneficial and which cause IBD. “The long-term objective is to develop a vaccine or find ways to get rid of the bad bacteria,” Dr. Cominelli says.

Maneesh Dave, MD, MPH, Attending Gastroenterologist, UH Cleveland Medical Center and Assistant Professor of Medicine, Case Western Reserve University School of Medicine, uses mesenchymal and intestinal stem cells for creating “mini-guts” in the laboratory to identify new therapies and for personalized treatment of patients with IBD.

A large Phase III clinical trial published in highly regarded journal The Lancet studied stem cell therapy for perianal fistulas in Crohn's disease patients who have not responded well to conventional IBD therapies. About half the patients treated with stem cells achieved remission, which is one reason why UH is further investigating stem cells in mouse models, Dr. Dave explains.

Working with mouse models, Dr. Dave uses human mesenchymal stem cells isolated from bone marrow to suppress inflammation and regenerate intestinal lining damaged after inflammation. He is working on different strategies to enhance the healing and regenerative potential of these cells.

“The ultimate goal would be to optimize these cells for each patient's treatment based on their unique disease pathophysiology,” Dr. Dave says. “We could get cells from a healthy donor, or healthy cells from an IBD patient, tailor them for an individual patient, and inject the cells to treat IBD.”

CLINICAL TRIALS

Anti-inflammatory, immunosuppressive drugs, biologic therapies and dietary changes are a few ways doctors help patients manage IBD symptoms. In addition, IBD specialists at UH Digestive Health Institute direct and participate in numerous clinical trials to bring new and better treatments to patients.

One current multicenter diet trial compares the Mediterranean diet to a specific carbohydrate-free diet. The findings will help doctors better advise patients on nutritional strategies to manage and reduce IBD symptoms.

Another clinical study being done in collaboration with Center for Computational Imaging at Case Western Reserve University is using artificial intelligence (AI) to predict patient outcomes and response to treatment by studying magnetic resonance enterography (MRI) images. “We extract radiomic features from MRI images and computer analysis to predict which IBD patients will need surgery and who will respond to drug therapy,” Dr. Dave says.

The UH Digestive Health Institute also plans to lead a promising new clinical trial for patients with ulcerative colitis. The trial, led by Dr. Cominelli, will study the effect of treatment with a novel anti-IL 1 antibody on the disease.

THE INFLAMMATORY BOWEL DISEASE CENTER

Specialists at the Inflammatory Bowel Disease Center at UH Digestive Health Institute — including gastroenterologists, colorectal surgeons, gastrointestinal pathologists, radiologists and nurse practitioners — use the latest therapies to diagnose and manage IBD. These therapies include biologic, non-biologic and new small molecule treatments.

“Our services complement our robust science program,” says Jeffry Katz, MD, Medical Director, Inflammatory Bowel Disease Center, UH Cleveland Medical Center and Professor of Medicine Case Western Reserve University School of Medicine. “For example, we use a patient-based biorepository to collect blood and tissue samples, which provides patient samples that will help our scientists better understand these illnesses.”

IBD affects each patient differently – and each patient responds to treatment differently. For those reasons, the Inflammatory Bowel Disease Center takes a personalized treatment approach with close and careful evaluation, treatment planning and follow-up.

“We offer patients the full spectrum of available approved therapies, with an effort to avoid exposure to steroid treatments and minimize disease complications, as well as access to experimental new drugs,” Dr. Katz explains. “We're aggressive in our approach to achieve the best outcomes for our patients.”

That approach includes offering ongoing programs for cancer risk surveillance, such as chromoendoscopy.
Individuals with longstanding ulcerative colitis face an increased colorectal cancer risk, and those with Crohn's disease have an increased rate of intestinal cancer, including both colon and small bowel sites.

Other advanced endoscopic and non-endoscopic imaging techniques also help doctors more accurately assess disease location and severity. Moving forward, the Inflammatory Bowel Disease Center will be initiating additional studies into the effects of complementary therapies, including mindfulness training, on IBD symptoms.

CONTINUED PROGRESS

UH Digestive Health Institute inflammatory bowel specialists continue to research the most effective treatments and management protocols for patients suffering from IBD. As progress continues, the department hopes to develop new treatments and eventually a cure for these debilitating, chronic conditions.

To refer a patient to a digestive health specialist, call 1-800-552-8338 or 216-844-7553.