Primary Sclerosing Cholingitis (PSC)
Primary sclerosing cholangitis (PSC) is a rare, heterogeneous, idiopathic, inflammatory disorder of the bile ducts resulting in strictures of the intrahepatic and /or extrahepatic bile ducts. Although the great majority of PSC patients have inflammatory bowel disease (IBD), only ~ 5% of IBD patients will develop PSC, the underlying causes of the association remaining poorly understood. PSC affects all age groups and has been described in a variety of ethnic and racial groups but is best characterized in populations of Northern European descent. PSC has a male predominance (2:1); and although it may occur at any age, it has a diagnostic peak at 30–40 years. Women tend to be diagnosed later at an average age of approximately 45 years.
Primary sclerosing cholangitis and Galanin
Galanin was first isolated in 1983 and is relatively new with an evolving understanding of its functions in humans. Galanin’s central nervous system (CNS) actions—and in particular its proposed role in Alzheimer's disease—have helped to fuel interest in galanin. The late introduction of specific, high-affinity galanin antagonists in 1991 made it possible to study the role of endogenous galanin—which often appears as a strong tonic inhibitor of neuronal actions, a feature studied best by use of antagonists. Within the central nervous system, highest concentrations are found in the hypothalamus, with lower levels in the cortex and brainstem. It is widely distributed in the gastrointestinal system particularly in the liver and intestines.
Galanin receptor inhibitor (ST-003) in treating PSC
The goals of PSC treatment are to halt the impact of excessive galanin concentrations that increase cholangiocyte proliferation and fibrogenesis as is found in humans as well as in the Mdr2KO murine model. Gal1 and Gal2 antagonism in the Mdr2KO has resulted in reduced bile duct mass and hepatic fibrosis. ST-003 portends to be an important treatment as it has the ability to meet the treatment goals by addressing a host of disease factors found in the PSC complex, multifactorial disease state.