In April 1994, the largest outbreak of botulism in the United States since 1978 occurred in El Paso, Texas. Thirty people were affected; 4 required mechanical ventilation. All ate food from a Greek restaurant. The attack rate among people who ate a potato-based dip was 86% (19/22) compared with 6% (11/176) among people who did not eat the dip (relative risk [RR] = 13.8; 95% confidence interval [CI], 7.6–25.1). The attack rate among people who ate an eggplant-based dip was 67% (6/9) compared with 13% (24/189) among people who did not (RR = 5.2; 95% CI, 2.9–9.5). Botulism toxin type A was detected in patients and in both dips. Toxin formation resulted from holding aluminum foil-wrapped baked potatoes at room temperature, apparently for several days, before they were used in the dips. Food handlers should be informed of the potential hazards caused by holding foil-wrapped potatoes at ambient temperatures after cooking. In 2002, fourteen Alaskans ate muktuk (whale blubber) from a beached whale, resulting in eight of them developing botulism, with two of the affected requiring mechanical ventilation. Beginning in late June 2007, 8 people contracted botulism poisoning by eating canned food products produced by Castleberrys Food Company in its Augusta, Georgia plant. It was later identified that the Castleberrys plant had serious production problems on a specific line of retorts that had under-processed the cans of food. These issues included broken cooking alarms, leaking water valves and inaccurate temperature devices, all the result of poor management of the company.
Obeticholic acid (OCA), sold under the brand name Ocaliva, is a semi-synthetic bile acid analogue which has the chemical structure 6α-ethyl-chenodeoxycholic acid. It is used as a medication used to treat primary biliary cholangitis. Intercept Pharmaceuticals Inc. hold the worldwide rights to develop OCA outside Japan and China, where it is licensed to Dainippon Sumitomo Pharma. Invention and development
The natural bile acid chenodeoxycholic acid was identified in 1999 as the most active physiological ligand for the farnesoid X receptor (FXR), which is involved in many physiological and pathological processes. A series of alkylated bile acid analogues were designed, studied and patented by Roberto Pellicciari and colleagues at the University of Perugia, with 6α-ethyl-chenodeoxycholic acid emerging as the most highly potent FXR agonist. FXR-dependent processes in liver and intestine were proposed as therapeutic targets in human diseases. Obeticholic acid is the first FXR agonist to be used in human drug studies. Clinical studies
Obeticholic acid is undergoing development in phase II and III studies for specific liver and gastrointestinal conditions. The U.S. Food and Drug Administration (FDA) approved obeticholic acid on May 27, 2016, for the treatment of primary biliary cholangitis. It was approved as an orphan drug based on its reduction in the level of the biomarker alkaline phosphatase as a surrogate endpoint for clinical benefit. It is indicated for the treatment of primary biliary cholangitis in combination with ursodeoxycholic acid in adults with an inadequate response to UDCA, or as monotherapy in adults unable to tolerate UDCA.