Therapeutic Focus

Ocera’s therapeutic focus is on gastrointestinal and liver diseases. Our initial target indications are in Inflammatory Bowel Disease, specifically Crohn’s disease, Irritable Bowel Syndrome, and Hepatic Encephalopathy.

IBD

Inflammatory Bowel Disease represents a group of disorders characterized by chronic inflammation affecting the gastrointestinal tract. The two most common Inflammatory Bowel Disease conditions are Crohn’s disease and Ulcerative Colitis. The Crohn’s disease population in the U.S. is estimated to be more than 500,000, and is expected to grow at 3 percent annually. The worldwide population of Inflammatory Bowel Disease is estimated to be over 4 million.

The segments of the gastrointestinal tract most often affected by Crohn’s are the small intestine, the large intestine (also called the colon), and the rectum. Unlike ulcerative colitis, in which inflammation and ulceration are limited to the mucosal and submucosal layers of the colon and rectum, the inflammation and ulceration of Crohn’s disease can extend through all layers of the intestinal wall. Common symptoms of the disease include diarrhea, abdominal pain, weight loss and complications such as intestinal abscesses, fistulas, and intestinal obstructions. The course of Crohn’s disease is intermittent, with disease exacerbations followed by periods of remission. Up to 30 percent of patients with Crohn’s disease have been reported to suffer from fistulas. Crohn’s disease is a debilitating and chronic condition. Fistulas represent a frequent complication of Crohn’s disease, and have a major impact on patients’ quality of life and often require surgical intervention.

For more information on IBD, please check: www.ccfa.org

IBS

Irritable Bowel Syndrome is one of the most commonly recognized functional gastrointestinal diseases. Experts estimate that nearly 20 percent of the world’s population suffers from a combination of altered bowel function (i.e., diarrhea, constipation, or alternation of the two) and abdominal pain that is the hallmark of Irritable Bowel Syndrome. The condition affects 25 to 55 million people in the US. 2.5 to 3.5 million yearly visits to physicians and 20-40 percent of visits to gastroenterologists are due to symptoms of IBS.

For more information on IBS, please check:  www.iffgd.org

HEPATIC ENCEPHALOPATHY

Hepatic encephalopathy is due to failure to metabolize neurotoxic substances with resulting alterations of astrocyte morphology and function. The pathophysiology involves increased levels of ammonia, which in turn result in up-regulation of astrocytic peripheral benzodiazepine receptors (PBR).  Other neurotoxins include short-chain fatty acids, mercaptans, oxindol phenol, quinolinic acid, tryptophan, serotonin, dopamine, catecholamine. These compounds are directly toxic to neurons or glia, and their encephalopathogenic potency may be synergistically enhanced by ammonia.  In addition to glutamatergic synaptic dysfunction, abnormalities in other neurotransmitter systems, including the dopaminergic and the histaminergic systems, have also been reported in HE. Tryptophan, precursor of serotonin, and serotonin are elevated in the blood, cerebrospinal fluid (CSF), and brain tissue of patients with HE [Jones 2000¹, Ong 2003²].

Lactulose, which has become the standard of care in hepatic encephalopathy.  Despite its multiple mechanisms of action, lactulose has not proven to be of consistent benefit over placebo, especially in larger multi-center trials. [Als-Nielsen, 2004³].  In addition, the drug is not well tolerated due to gastrointestinal side-effects; this jeopardizes treatment compliance.

PPI(Proton Pump Inhibitor) resistant GERD

GERD is caused by a hypotonic lower esophageal sphincter or transient lower esophageal sphincter relax ations that allow gastric content to reflux back into the esophagus.  Some factors that may exacerbate GERD symptoms include hiatal hernia, obesity, smoking, caffeine, fatty foods, and chocolate.  Esophagitis from the acid refluxate can reduce the normal motility of stomach contents and damage the esophageal tissue lining.  In the United States and Europe, 30-45% of adults experience heartburn or acid regurgitation (the primary symptoms of gastroesophageal reflux disease [GERD]) at least once per month; 12-13% experience these symptoms frequently, or at least once per week.  [Ryan, 2003⁴].  Proton Pump Inhibitors are the current gold standard for treating GERD symptoms.  However, it is believed that up to 15% of the population do not respond to PPI, and there are no other alternative treatments available to treat these patients. 

The importance of duodenogastric reflux of bile acids into the esophagus has been recently assessed by Xu et al, who found that patients with reflux esophagitis had more frequent and more prolonged bile reflux episodes than patients with non-erosive reflux disease. They also recommended combining pH and bilirubin monitoring in identifying patients at risk for complications.

Pouchitis

An Ileal Pouch Anal Anastomosis (IPAA) is a surgical procedure by which the small intestine is used to create an internal pouch as a reservoir for stool after colectomy. Often, presumably as a result of a shortened bowel and change in bacterial flora composition and/or bile acid composition, the lining of this internal pouch becomes inflamed. Pouchitis can cause symptoms similar to ulcerative colitis, such as diarrhea, cramping abdominal pain, increased frequency of stool, bleeding, fever, dehydration and joint pain. The condition may be managed with a short course of anti-infectives, but relief can be short lived and the inflammation can become recurrent or chronic.

Although patients respond to antibiotics, they can become chronically antibiotic dependent.  Additionally, antibiotics such as metronidazole can be associated with adverse effects such as neuropathy that may not be reversible [Shen, 2003a⁵; Sandborn, 1997⁶].   No drugs are currently approved for the treatment of pouchitis. Anti-infectives (ciprofloxacin, metronidazole) are the most commonly prescribed treatments, but there is limited long term data on the use of antibiotics and chronic exposure can be associated with development of antibiotic resistance. Of patients with acute pouchitis, 61% will develop at least one recurrence [Lohmuller, 1990⁷].