Regeneron Confirms New Chronic Liver Disease Drug Target Using Biobank Data

The Liver. Source: OpenClipart-Vectors, no changes made, CC0 Creative Commons
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For the first time Regeneron has reported a variant in the HSD17B13 gene that is associated with reduced risk of, in other words protection from, various chronic liver diseases for which there are currently no approved therapeutics [1]. The company did this by analyzing extensive genetic sequencing data linked with electronic health records. Much of the sequenced data relies on biobanked materials. Scientists from the Regeneron Genetics Center (RGC) discovered HSD17B13 as a potential new therapeutic target to reduce the risk of chronic liver disease and progression to more advanced stages of disease, such as nonalcoholic steatohepatitis (NASH).

A Homozygous loss-of-function variant in the HSD17B13 gene, which encodes the hepatic lipid droplet protein hydroxysteroid 17-beta dehydrogenase 13, resulted in a 73 percent lower risk of alcoholic cirrhosis and 49 percent lower risk of nonalcoholic cirrhosis than homozygous functioning HSD17B13. This homozygous variant was also associated with a 53 percent lower risk of alcoholic liver disease and 30 percent lower risk of nonalcoholic liver disease. NASH risk was also reduced, suggesting that loss of HSD17B13 function protects from progression to later stages of liver disease.

The findings were originally made by studying the exome sequence data and corresponding electronic health records of more than 46,544 participants in the DiscovEHR study population from the MyCode® Community Health Initiative at the Geisinger Health System. The results were confirmed in analyses of additional populations: 2,644 additional individuals from the DiscovEHR population who had undergone bariatric surgery, 1,357 individuals from the Dallas Heart Study and 8,526 individuals from the Penn Medicine Biobank, 517 people in the multi-ethnic Dallas Liver and Heart Studies and 439 Hispanic American children in the Dallas Pediatric Liver Study.

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“These findings further emphasize the importance of large-scale human genetics data in drug discovery, and represent yet another actionable breakthrough coming from the Regeneron Genetics Center,” said George Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer of Regeneron.

Based on these findings, Regeneron has established a collaboration with Alnylam Pharmaceuticals, Inc. to discover RNAi therapeutics for HSD17B13 [2, 3].



  1. Abul-Husn NS, et al. A Protein-Truncating HSD17B13 Variant and Protection from Chronic Liver Disease. N Engl J Med. 2018 378(12):1096-1106. doi: 10.1056/NEJMoa1712191. PubMed PMID: 29562163.