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Methods of treating fatty liver disease with helminth-derived glycan-containing compounds

A fatty liver disease, a technology of compounds, applied in the field of treating diseases related to the accumulation of fat in the liver, preventing diseases related to the accumulation of fat in the liver, can solve problems such as aggravation of deficiency

Inactive Publication Date: 2014-07-30
PRESIDENT & FELLOWS OF HARVARD COLLEGE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

This problem is further exacerbated by a lack of clear understanding of the pathogenesis involved in these diseases

Method used

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  • Methods of treating fatty liver disease with helminth-derived glycan-containing compounds
  • Methods of treating fatty liver disease with helminth-derived glycan-containing compounds
  • Methods of treating fatty liver disease with helminth-derived glycan-containing compounds

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Embodiment Construction

[0048]Prior to the present invention, compounds containing Lewis antigens (such as LNFPIII) were known to be able to modulate cytokine production (such as IL-10, IL-4 and IL-5) by immune cells that allow Th1 or Th2 responses The developmental deviation of , a response known to be critical for the development and progression of many disease states, such as autoimmune diseases, cancer and infectious diseases. For example, stimulatory forms of Lewis antigen compounds have been shown to elicit an antigen-specific immune response (IgG response), while inhibitory forms suppress allergic responses (IgE responses) (see, e.g., U.S. Pat. Nos. 6,540,999, 6,841,543, and 7,799,755). However, the role of Lewis antigen-containing compounds (eg LNFPIII) in other clinical aspects and the signaling pathways targeted by these compounds are largely unknown.

[0049] Accordingly, the present invention is based, at least in part, on the unexpected discovery that compounds comprising helminth-derive...

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Abstract

The present invention provides a compound comprising a helminth-derived glycan and / or glycoconjugate thereof (e.g., a compound comprising a Lewisx antigen (e.g., LNFPIII), a non-Lewisx antigen (e.g., LNnT, LDN, and LDN derivatives), or a mixture of Lewisx and non-Lewisx antigens (e.g., SEA)), useful as a therapeutic compound for treating or preventing diseases associated with fat accumulation in the liver. The compounds of the invention are useful for treating or preventing the development of a fatty liver disease in a subject that has the disease or is at risk of developing the disease, and inhibiting lipogenesis in hepatocytes.; The invention also provides methods of regulating the Erk-c-fos / AP-1-FXRalpha signalling pathway by administering a compound comprising a helminth-derived glycan and / or glycoconjugate thereof to a subject with a fatty liver disease, or contacting a hepatocyte with a compound comprising a helminth-derived glycan and / or glycoconjugate thereof.

Description

[0001] related application [0002] This application claims U.S. Provisional Application No. entitled "Methods of Treating Fatty Liver Disease with Helminth-Derived Glycan-Containing Compounds," filed September 23, 2011. Priority of 61 / 538629, the entire contents of which are incorporated herein by reference. Background of the invention [0003] Diseases characterized by the accumulation of fat in the liver are becoming more prevalent among adults and children in industrialized countries, largely due to unhealthy eating habits and obesity. Alcoholic fatty liver disease (AFLD), caused by chronic excessive alcohol consumption, essentially follows a pathological process involving steatosis, steatohepatitis (ASH), inflammation, cirrhosis, and in some cases, hepatocellular carcinoma. Non-alcoholic fatty liver disease (NAFLD), considered the most common liver disease, is a term encompassing a spectrum of liver pathologies similar to AFLD, ranging in severity from hepatocellular ste...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K48/00A61K38/17A61K38/16A61K31/726A61P1/16A61P1/00
CPCA61K31/726A61K35/62A61K47/61A61K47/64A61P1/00A61P1/16
Inventor C-H.李P.巴尔加瓦D.A.哈恩
Owner PRESIDENT & FELLOWS OF HARVARD COLLEGE
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