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Selectively Targeting Sphingosine-1-Phosphate Receptors (S1PRs) to Treat Liver Diseases

詳細技術說明
The inventors have discovered a new therapeutic target for the treatment of liver diseases, such as liver fibrosis and liver cirrhosis.
*Abstract

TechnologyOverview

Liver diseases that lead to theformation of scar tissue (fibrosis) and cirrhosis are often lethal, and comewith few treatment options. Stimulating regeneration of liver tissue couldprovide a novel therapeutic option. Liver has the capacity to regenerate itselffollowing damage or injury. However, this process is frequently impairedresulting in fibrosis and cirrhosis.

The inventors found that selectivetargeting of the sphingosine-1-phosphate receptor (S1PR), found in the livervasculature system, aids the regenerative process, promotes liver repair andblocks fibrosis. They also found that treatment of injured liver tissue withthe S1PR1-selective pharmacological agonist SEW2871 restored liver function andreduced the formation of scar tissue. Hence, selectively targetingpharmacologically active S1PRs can provide much-needed treatment options forfibrosis-related liver diseases.

Potential Applications

· Treatment of liver fibrosis-related diseases, includinginfection-mediated hepatic cirrhosis and non-alcoholic fatty liver diseases(NAFLD)

· Treatment of other fibrosis-related diseases such as,idiopathic pulmonary fibrosis and kidney fibrosis

Advantages

· S1PR is a druggable molecular target that belongs to theG-protein coupled receptor (GPCR) family, which has been shown to be highlyaccessible to administered agents. Their ligand-receptor pharmacology has alsobeen extensively characterized.

· S1PR is preferentially expressed by the liver vascularsystem during regeneration, making it highly accessible to intravenouslyinjected therapeutics, with optimal biodistribution and pharmacodynamics.

*Licensing
Dan-Oscar Antsonda429@cornell.edu646-962-7042
其他

HDL activation ofendothelial sphingosine-1-phosphate receptor-1 (S1P1) promotes regeneration andsuppresses fibrosis in the liver. Bi-Sen Ding et. al., JCI Insight. 2016 Dec 22; 1(21): e87058.

國家/地區
美國

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