Curing Crohn’s

Written by Safwan Haque | SQ Staff Writer | SQ Online (2013-14)

Saying Crohn’s disease is painful may be an understatement. Imagine the feeling of piranhas gnawing at your insides and you may start to understand the nature of the disease. Crohn’s is an inflammatory autoimmune disease of the bowel. The areas affected by Crohn’s are usually the intestines but may be anywhere between the mouth to the anus. According to the National Medical Library of the United States, Crohn’s is believed to have no cure. However, Dr. William Sandborn and his team of researchers have discovered a new drug, Vedolizumab, to fight the disease.

The exact causes for Crohn’s is still unknown but it happens when the body’s defense mistakenly attacks and destroys healthy body tissues. Genes, family history, one’s environment, smoking, and the body’s tendency to overreact to gut bacteria seem to play a role in Crohn’s disease. There are several symptoms, including fever and weight loss. The symptoms can be reduced through a multitude of pain medicine and having a good, healthy diet plan with fiber supplements. In extreme cases damaged portions of the gut may need to be removed.

Dr. Sanborn’s involvement with Crohn’s starts more than 10 years ago. He looked at MAdCAM-1, which is a blood vessel lining cell adhesion molecule that interacts with the white blood cell (leukocyte) beta 7 integrin on bone marrow tissue cells to let healing leukocytes into mucosal and inflamed tissues such as that seen in Crohn’s. Also of interest was, VCAM-1 or Vascular cell adhesion protein 1. This is a cell adhesion molecule that is expressed on blood vessels after endothelial cells are stimulated by cytokines, which are inflammatory proteins of the immune system that are used for cell signalling.

UCSD Medicine
Dr. William Sanborn. Courtesy of UCSD School of Medicine.

“I was involved with clinical trials with a monoclonal antibody to alpha 4 integrin (blocks both alpha 4 beta 1/VCAM and alpha 4 beta 7/ MAdCAM-1) called natalizumab (Tysabri)”, said Dr. Sandborn.

According to Dr. Sandborn, Natalizumab has not been used because it is associated with binding to alpha 4 beta 1/VCAM that may assist in brain infection from the JC polyoma virus. Infection with this virus can result in a deadly disease called progressive multifocal leukoencephalopathy (PML). Thus, he went forward with a different approach.

“Since alpha 4 beta 7/MAdCAM-1 is selective for the gastrointestinal tract, a selective antibody to alpha 4 beta 7 could potentially achieve the benefit of natalizumab, without the risk of PML.” said Dr. Sandborn.

Recently, Vedolizumab, a new drug found by Dr. Sandborn and his team of researchers at the University of California, San Diego (UCSD) School of Medicine has offered hope for treating Crohn’s disease. Vedolizumab is a human monoclonal antibody that binds to specific integrins. Integrins are cell membrane receptors that create the attachments between cells to form tissues such as the lining of our stomach and our skin. Alpha four chain integrins associate with either beta four or beta seven integrin chains. These integrin protein chains are recognized as antigens – targets for immunoglobulins or antibodies (part of the immune system). A monoclonal antibody like vedolizumab binds to the same binding region of the same target antigen (proteins like alpha 4 beta 7).

A comparative drug study was performed with Vedolizumab and a placebo drug (control). It was found that Vedolizumab only acts on the digestive tract and suppresses immune system cells that release proteins call cytokines to cause inflammation in parts of the tract. Fortunately, there have been no major side effects as caused by other drugs such as steroids and immunosuppressive medication. The entire study lasted 52 weeks “in which complete healing of the bowel was observed and maintained with continued use of Vedolizumab” said Dr. Sandborn.

In the future, Dr. Sandborn hopes to see additional studies looking at more intensive (higher dose) induction therapy, treatment of patients with more newly diagnosed disease and studies using colonoscopy to determine if vedolizumab heals the intestine in patients with Crohn’s disease. No side effects are foreseen by Dr. Sandborn although that possibility always exists in drug studies.

Principal investigator William Sandborn and his colleagues have added on to UCSD School of Medicine’s credits as a national entity in leading medical research. Now patients have a chance to fight this critical disease that affects over half a million people every year in the United States alone and has prevailed for so long without a solution.