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©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 21, 2017; 23(23): 4181-4190
Published online Jun 21, 2017. doi: 10.3748/wjg.v23.i23.4181
Published online Jun 21, 2017. doi: 10.3748/wjg.v23.i23.4181
Anti-steatotic and anti-fibrotic effects of the KCa3.1 channel inhibitor, Senicapoc, in non-alcoholic liver disease
Latha Paka, David E Smith, Dawoon Jung, Siobhan McCormack, Ping Zhou, Bin Duan, Jing-Song Li, Jiaqi Shi, Yong-Jie Hao, Kai Jiang, Michael Yamin, Itzhak D Goldberg, Prakash Narayan, Department of Research and Development, Angion Biomedica Corp., Uniondale, NY 11553, United States
Author contributions: Paka L, Yamin M, Goldberg ID and Narayan P substantially contributed to the conception and design of the study, acquisition, analysis and interpretation of data; Narayan P drafted the article related to the intellectual content of the manuscript; and Paka L made revisions for the final version of the article to be published; Jung D performed image analysis using Image J Program. All other authors contributed for performing all the technical aspects of in vitro and in-vivo work; McCormack S and Zhou P performed in vitro work; Smith DE, Duan B, Li JS, Shi J, Hao YJ and Jiang K performed animal care, experimental dosing, pre and post-surgical procedures in animal models.
Institutional animal care and use committee statement: Angion’s Animal Welfare Assurance # A4532-01. All the study protocols were designed to minimize pain and distress to the animals and were reviewed approved by our Angion’s animal care and use committee.
Conflict-of-interest statement: To the best of our knowledge, no conflict of interest exists.
Data sharing statement: Angion Biomedica is a for-profit small business engaged in developing therapeutics for unmet medical needs. In keeping with corporate policy, data and research resources generated by the company are proprietary. Once all intellectual property that results from the generation of the data and research resources is protected via filing of patents, data and research resources generated will be made available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Latha Paka, PhD, Senior Research Scientist, Department of Research and Development, Angion Biomedica Corp., 51 Charles Lindbergh Blvd, Uniondale, NY 11553, United States. spaka@angion.com
Telephone: +1-516-3261200 Fax: +1-516-3071659
Received: November 18, 2016
Peer-review started: November 21, 2016
First decision: January 19, 2017
Revised: February 4, 2017
Accepted: April 13, 2017
Article in press: April 13, 2017
Published online: June 21, 2017
Peer-review started: November 21, 2016
First decision: January 19, 2017
Revised: February 4, 2017
Accepted: April 13, 2017
Article in press: April 13, 2017
Published online: June 21, 2017
Core Tip
Core tip: Given the large numbers of people with fatty livers and even relatively indolent steatosis can result in a significant population progressing to non-alcoholic steatohepatitis (NASH), NASH with fibrosis and cirrhosis. We report for the first time that a KCa3.1 channel inhibitor exerts an anti-steatotic effect in the setting of fatty liver disease which can be harnessed for the treatment of liver fibrosis. Second, we are the first to report that Senicapoc, a drug that has been through Phase III clinical trials, can be repurposed for the treatment of fatty liver disease and potentially for the treatment of other lipid disorders.