Discovery of Genetic Mutation Could Lead to New Treatment for Alcoholic Liver Disease

Discovery of Genetic Mutation Could Lead to New Treatment for Alcoholic Liver Disease

A study conducted at the Regeneron Genetics Centre of Regeneron Pharmaceuticals Inc., has uncovered a genetic mutation that protects against liver cirrhosis. If new medicines could be developed that mimic the genetic mutation, they could be used as a novel new treatment for alcoholic liver disease.

Cirrhosis from long-term damage to the liver from excessive alcohol consumption is a leading cause of death. In the UK, more than 4,000 people die from cirrhosis each year and in the United States, there are 88,000 deaths from alcohol-related liver disease and cirrhosis. The only hope for patients is a liver transplant.

The study used genome data from more than 46,000 patients who participated in the DiscovEHR human genetics study to identify potential genetic factors that influence levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) – two common markers of liver health.

The researchers determined that a splice variant in the HSD17B13 gene – which codes for the enzyme hydroxysteroid 17-beta dehydrogenase 13 which is involved in lipid metabolism – was associated with lower levels of ALT and AST, and a reduced risk of alcoholic liver disease.

The genetic mutation results in instability and degradation of the hydroxysteroid 17-beta dehydrogenase 13 enzyme. The researchers discovered there was a 73% lower chance of patients developing cirrhosis from heavy alcohol use when they did not have a working copy of the HSD17B13 gene and there was half the risk of developing cirrhosis from other causes such as obesity and hepatitis B and C infections.

Regeneron has partnered with Alnylam Pharmaceuticals and is searching for gene silencing drugs that could mimic the gene mutation for use as a new treatment for alcoholic liver disease.

The research is detailed in the paper – A Protein-Truncating HSD17B13 Variant and Protection from Chronic Liver Disease – recently published in The New England Journal of Medicine.

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