Chronic Cognitive Impairment in Cholestatic Liver Disease: Impact, Pathogenesis, Treatment and Relevance to Dementia
Principal Investigator: Professor David Jones
To develop the essential tools to allow us to explore the utility of early OCA as a transformative treatment for cholestatic cognitive impairment.
People normally associate memory and concentration problems (“cognitive symptoms”) with dementia. They can, however, also be a real problem in some patients with chronic diseases seemingly unrelated to dementia. Primary Biliary Cholangitis (PBC) is a chronic disease of the liver in which the bile ducts (which normally drain bile out of the liver and into the bowel) are damaged by the immune system. This causes reduction of bile flow and build up of bile within the body. PBC patients can get severe symptoms which can badly affect their quality of life. The most important of these are cognitive symtpoms accompanying profound fatigue (present in up to half of patients). To date there is no treatment.
The Newcastle team have been working for a number of years with the PBC Foundation, a national patients group, to understand this problem and to treat it. Recently we have found, that mice with poor bile flow also experieicne cognitive problems and fatigue, that there is a build up of bile in the brain, and that this is to an extent poisonous to the brain causing the brain symtoms. Critically, both the symtpoms and the brain poisoning are reversed completely with a new drug called Obeticholic Acid (Ocaliva). This offers real potential as a new treatment for the symtpoms of PBC
This BRC project will allow us to identify the ways to best monitor symptoms and brain change in PBC in practice, and to explore for the first time in PBC patients whether Ocaliva can treat brain change and symtpoms in humans with poor bile flow as it does in mice.