US 12,215,322 B2
Treatment of liver disease with mitochondrial glycerol-3-phosphate acyltransferase (GPAM) inhibitors
Luca Andrea Lotta, Tarrytown, NY (US); Niek Verweij, Tarrytown, NY (US); Colm O'Dushlaine, Tarrytown, NY (US); Jonathan Marchini, Tarrytown, NY (US); and Aris Baras, Tarrytown, NY (US)
Assigned to Regeneron Pharmaceuticals, Inc., Tarrytown, NY (US)
Filed by Regeneron Pharmaceuticals, Inc., Tarrytown, NY (US)
Filed on Feb. 25, 2022, as Appl. No. 17/680,940.
Claims priority of provisional application 63/154,693, filed on Feb. 27, 2021.
Prior Publication US 2022/0307032 A1, Sep. 29, 2022
Int. Cl. C12N 15/11 (2006.01); A61K 31/7088 (2006.01); A61K 38/46 (2006.01); A61P 1/16 (2006.01); C12N 15/113 (2010.01); C12Q 1/6883 (2018.01); C12Q 1/6827 (2018.01); C12Q 1/6874 (2018.01)
CPC C12N 15/1137 (2013.01) [A61K 31/7088 (2013.01); A61K 38/465 (2013.01); A61P 1/16 (2018.01); C12Q 1/6883 (2013.01); C12N 2310/14 (2013.01); C12N 2310/531 (2013.01); C12Q 1/6827 (2013.01); C12Q 1/6874 (2013.01); C12Q 2600/156 (2013.01); C12Q 2600/158 (2013.01)] 3 Claims
 
1. A method of treating a subject having liver disease or at risk of having liver disease, having fatty liver disease or at risk of having fatty liver disease, having hepatocellular carcinoma or at risk of having hepatocellular carcinoma, having liver cirrhosis or at risk of having liver cirrhosis, having liver fibrosis or at risk of having liver fibrosis, and/or having simple steatosis, steatohepatitis, or non-alcoholic steatohepatitis (NASH) or at risk of having simple steatosis, steatohepatitis, or NASH, the method comprising administering a glycerol-3-phosphate acyltransferase (GPAM) inhibitor to the subject, wherein:
the GPAM inhibitor comprises an antisense nucleic acid molecule, a small interfering RNA (siRNA), or a short hairpin RNA (shRNA) that hybridizes to a GPAM mRNA; and
the subject is heterozygous for a GPAM predicted loss-of-function variant mRNA molecule comprising SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, and/or SEQ ID NO: 14.