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Pharmaceutical composition for improving or treating autosomal dominant polycystic kidney disease comprising dna methylation inhibitor

A methylation inhibitor, autosomal technology, used in gene therapy, carbohydrate active ingredients, chemical instruments and methods, etc., can solve the problems of lack of analysis, negative feedback obstacles, disappointing clinical results, etc.

Active Publication Date: 2018-01-02
SOOKMYUNG WOMENS UNIV IND ACADEMIC COOPERATION FOUND
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there is no DNA methylation profiling analysis of the global epigenome or autosomal dominant polycystic kidney disease
[0005] Although many drugs for treating polycystic kidney disease have been developed so far, disappointing clinical results have been obtained due to the hindrance of negative feedback

Method used

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  • Pharmaceutical composition for improving or treating autosomal dominant polycystic kidney disease comprising dna methylation inhibitor
  • Pharmaceutical composition for improving or treating autosomal dominant polycystic kidney disease comprising dna methylation inhibitor
  • Pharmaceutical composition for improving or treating autosomal dominant polycystic kidney disease comprising dna methylation inhibitor

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Embodiment Construction

[0077] The present invention provides a pharmaceutical composition for improvement or treatment of autosomal dominant polycystic kidney containing DNA methylation inhibitor.

[0078] The above-mentioned DNA methylation inhibitor is not particularly limited but is expected to be characterized by 5-aza-dC (5-aza-2'-deoxycytidine) or zebularine.

[0079] The composition of the present invention is one or more polycystic kidney treatment agents or used together with improving agents.

[0080] The composition of the present invention contains the above-mentioned active ingredients suitable for pharmacological and physiologically approved auxiliary agents, these auxiliary agents include excipients, disintegrants, sweeteners, binding agents, coating agents, bulking agents, lubricants, Slip modifiers or solubilizers, etc.

[0081] In addition, the composition of the present invention adds one or more pharmacologically permitted carriers in addition to the above-mentioned effective ingredients...

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Abstract

In order to determine the epigenetic mutation of autosomal dominant polycystic kidney disease and its functional relevance, the present inventors randomly analyzed the whole genome of polycystic kidney disease and non-polycystic kidney disease individuals by methylation profiling method and compared with their performance data. Interestingly, PKD1 and other genes associated with ion transport and cell binding were hypermethylated at the gene body, which was downregulated in polycystic kidney disease. In particular, PKD1 is partially hypermethylated in the polycystic kidney gene body, which is associated with MBD2 (methyl‑CpG‑binding domain 2) protein binding. Furthermore, DNA methylation inhibitor treatment was accompanied by an upregulation of PKD1 expression and delayed cyst formation in MDCK (Madin‑Darby Canine Kidney) cells. Thus, hypermethylation of PKD1 and cyst formation-associated regulatory genes of the present invention is decisive for cyst formation and revealed to be useful as a treatment for autosomal dominant polycystic kidney disease.

Description

Technical field [0001] The present invention relates to a pharmaceutical composition for improving autosomal dominant polycystic kidney disease, characterized in that the composition contains a DNA methylation inhibitor. Background technique [0002] The incidence of autosomal dominant polycystic kidney disease (ADPKD) is a more common genetic disease with at least 1 in every 500-1000. Compared with healthy people, autosomal dominant polycystic kidneys will form more fluid-filled cysts on both sides of the kidneys, and the kidneys will be 4-8 times larger. So far, most of the polycystic kidney disease will develop into end-stage renal disease (Gabow, 1993; Grantham, 1996) because there is no effective clinical treatment for polycystic kidney disease. The formation of cysts in human polycystic kidneys is accompanied by the cell proliferation and increase of the epidermal cells of the cysts and the self-destruction of the cells. [0003] Although inherited in an autosomal dominant ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/70A61K48/00A61K38/17A61K38/16
CPCA61K31/7068C07K14/47A61K31/70A61K38/16A61K38/17A61K48/00
Inventor 朴钟勋禹俞美金永峻裴宰范朴恩荣李善英辛裕彬
Owner SOOKMYUNG WOMENS UNIV IND ACADEMIC COOPERATION FOUND
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