Treatment of diseases associated with hepatic stellate cell activation using ammonia-lowering therapies
View Patent ↗Disclosed herein are methods of preventing, treating, and delaying the onset or progression of diseases associated with hepatic stellate cells (HSCs), such as non-alcoholic fatty liver disease (NAFLD), fibrosis, and liver cancer, using ammonia-lowering therapies.
1. A method of treating or delaying the onset or progression of a disease associated with hepatic stellate cell (HSC) activation, comprising administering one or more ammonia-lowering agents to a subject in need thereof, wherein the ammonia-lowering agent is selected from the group consisting of sodium phenylacetate, sodium phenylbutyrate (NaPBA), sodium benzoate, a laxative, an antibiotic, ornithine in combination with at least one of phenylacetate and phenylbutyrate, and any combinations thereof, wherein the disease associated with HSC activation is non-alcoholic fatty liver disease (NAFLD), liver cancer or liver fibrosis.
2. The method of claim 1 , wherein the disease associated with HSC activation is non-alcoholic fatty liver disease (NAFLD).
3. The method of claim 2 , wherein the NAFLD is non-alcoholic steatohepatitis (NASH).
4. The method of claim 2 , wherein the NAFLD is steatosis.
5. The method of claim 1 , wherein the disease associated with HSC activation is liver cancer.
6. The method of claim 1 , wherein the disease associated with HSC activation is liver fibrosis.
7. The method of claim 1 , wherein the ammonia-lowering agent is ornithine phenylacetate.
8. The method of claim 7 , wherein ornithine phenylacetate is administered in combination with a laxative.
9. The method of claim 1 , wherein the administration is oral, intravenous, intraperitoneal, intragastric, or intravascular administration.
10. The method of claim 9 , wherein the administration is intravenous or oral administration.
11. A method of preventing non-alcoholic fatty liver disease (NAFLD), comprising administering one or more ammonia-lowering agents to a subject in need thereof, wherein the ammonia-lowering agent is selected from the group consisting of sodium phenylacetate, sodium phenylbutyrate (NaPBA), sodium benzoate, a laxative, an antibiotic, ornithine in combination with at least one of phenylacetate and phenylbutyrate, and any combinations thereof.
12. The method of claim 11 , wherein the NAFLD is non-alcoholic steatohepatitis (NASH) or steatosis.
13. The method of claim 11 , wherein the ammonia-lowering agent is ornithine in combination with phenylacetate.
14. The method of claim 13 , wherein separate pharmaceutically acceptable salts of the ornithine and phenylacetate are administered to the subject.
15. The method of claim 14 , wherein phenylacetate is administered as sodium phenylacetate.
16. The method of claim 14 , wherein the ornithine is administered as a free monomeric amino acid or physiologically acceptable salt thereof.
17. The method of claim 13 , wherein the ornithine in combination with phenylacetate is administered as ornithine phenylacetate.
18. The method of claim 11 , wherein the administration is oral, intravenous, intraperitoneal, intragastric, or intravascular administration.
19. The method of claim 18 , wherein the administration is intravenous or oral administration.