A Therapeutic Trial of an Alpha-1 Adrenoceptor Antagonist in Fatty Liver Disease
Non alcoholic fatty liver disease (NAFLD) is now the most common cause of chronic liver disease in developed countries. There is at present no proven therapy for NAFLD. The population prevalence of NAFLD is ~25% with the prevalence of its more severe stage, of fatty liver with inflammation, non alcoholic steatohepatitis (NASH) at ~2.5%. The main therapeutic targets in NASH are arguably fibrogenesis and liver regeneration because in NASH hepatic stellate cells (HSC) – the liver’s principal fibrogenic cells are activated to deposit collagen and other matrix proteins and also because in NASH hepatocyte replication is inhibited secondary to increased oxidant stress. This replicative arrest of hepatocytes in NASH therefore necessitates expansion of the liver’s stem cell compartment to maintain the functional integrity of the liver. An ideal therapy in NASH should therefore be both anti-fibrotic and also expand the liver stem cell compartment to enhance liver repair.
| Date added | 24 Apr 2008 |
|---|---|
| Reference number | 60-034 |
| Status | The technology is protected by a patent family at the national stage. |
| Availability | Further Exemplification – Potential Wellcome Trust Translational Award |
| References | [Blank] |
The technology and its advantages
Over the last few years we have discovered and published compelling pre-clinical data on the involvement of the sympathetic nervous system (SNS) in liver repair in NASH. Experimental animals that lack SNS neurotransmitters are very poorly fibrogenic. Reconstitution experiments with SNS neurotransmitters in these animals normalises their response to NASH inducing agents. Moreover, HSC make norepinephrine, the principal SNS neurotransmitter and also express functional adrenoceptors. It is through these receptors that adrenoceptor antagonists act to reduce fibrogenesis both in culture cells and in whole animals. Besides reducing fibrosis, alpha-1 adrenoceptor antagonists also enhance liver regeneration through expansion of the liver progenitor cell compartment.
Market opportunity
The primary cause of NAFLD is insulin resistance secondary to obesity. Presently about 35% of the USA and 20% of the UK population is obese. The UK Department of Health predicts that by 2010, approximately 33% of the UK population will be obese. With rising rates of obesity therefore, rates of NAFLD are predicted to increase. In fact, at the current trajectory of obesity and NAFLD, NASH is predicted to overtake HCV infection as the leading cause of liver transplantation about a decade from now.
Further information
Please contact Dr Richard Fagan, UCL Business PLC T 020 7679 9000 E r.fagan@uclb.com
