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Pharmaceutical composition for alleviating 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 problems such as lack of analysis, disappointing clinical results, and negative feedback obstacles

Active Publication Date: 2015-12-16
SOOKMYUNG WOMENS UNIV IND ACADEMIC COOPERATION FOUND
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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 alleviating or treating autosomal dominant polycystic kidney disease comprising dna methylation inhibitor
  • Pharmaceutical composition for alleviating or treating autosomal dominant polycystic kidney disease comprising dna methylation inhibitor
  • Pharmaceutical composition for alleviating 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 improving or treating autosomal dominant polycystic kidney disease comprising a DNA methylation inhibitor.

[0078] The aforementioned 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 includes auxiliary agents suitable for pharmacy and physiologically acceptable besides the above-mentioned active ingredients, and these auxiliary agents include excipients, disintegrating agents, sweeteners, binding agents, coating agents, swelling agents, lubricants, Slip modifiers or solubilizers, etc.

[0081] Furthermore, the composition of the present invention can be formulated into a satisfactory pharmaceutical composition by adding one or ...

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Abstract

In order to determine epigenetic variations of autosomal dominant polycystic kidney disease and functional association therebetween, the present inventors have subjected individuals with polycystic kidney disease and without polycystic kidney disease to analysis through methylation profiling in random fashion of the genome as a whole. Interestingly, in PKD1 and other genes associated with ion transport and cell adhesion, there was hypermethylation in the gene-body region, and the expression of these genes was down-regulated in polycystic kidney disease. In particular, in PKD1, there was hypermethylation in the polycystic kidney disease gene-body region, and this was associated with MBD2 (methyl-CpG-binding domain 2) protein binding. In addition, DNA methylation inhibitor treatment was accompanied by up-regulation of PKD1 expression and caused a delay in cyst formation in MDCK (Madin-Darby Canine Kidney) cells. This therefore demonstrates that, in the present invention, hypermethylation of PKD1 and regulator genes associated with cyst formation plays a decisive role in cyst formation and shows that the present invention can be used in therapeutic applications for autosomal dominant polycystic kidney disease.

Description

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

Claims

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Application Information

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Patent Type & Authority Applications(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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