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Methods for preventing and treating chronic kidney disease (CKD)

a kidney disease and chronic kidney disease technology, applied in immunological disorders, metabolism disorders, antibody medical ingredients, etc., can solve the problems of periostin, fibrosis and ckd that cannot be addressed, and achieve the effect of preventing or reducing renal fibrosis

Inactive Publication Date: 2015-07-02
INST NAT DE LA SANTE & DE LA RECHERCHE MEDICALE (INSERM) +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

This patent discusses the use of different types of antibodies in gene therapy applications. These antibodies can be natural or non-natural, and can be engineered to reduce their immunogenicity in humans. The patent also mentions the use of adeno-viruses and adeno-associated viruses, which are safe and can be used to infect a wide range of cell types and species. The adeno-associated virus can also integrate into human cellular DNA in a specific way, which minimizes the risk of mutations and gene expression variability. Overall, this patent provides a technical solution for developing safe and efficient gene therapy methods.

Problems solved by technology

These studies however, did not address the issue whether or not periostin participates in the development of renal fibrosis and CKD.

Method used

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  • Methods for preventing and treating chronic kidney disease (CKD)
  • Methods for preventing and treating chronic kidney disease (CKD)
  • Methods for preventing and treating chronic kidney disease (CKD)

Examples

Experimental program
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Effect test

example 1

Periostin KO Mice are Protected Against the Development of CKD in an Experimental Tubulointerstitial Nephropathy (UUO Model)

[0090]Material & Methods

[0091]Animals:

[0092]Experiments were performed on wild type and periostin null mice (POSTN KO) donated kindly by S.J. Conway (Indianapolis, Ind.). These mice are characterized by the lack of the periostin gene and the replacement of the translation start site and the first exon by a lacZ reporter gene (ref). C57BL / 6 WT and POSTN KO female mice aged 4 to 6 months were used (n=9). Tubulointerstitial nephropathy model was induced by the unilateral ureteral obstruction (UUO). After induction of general anesthesia (intraperitoneal injection of pentobarbital 50 mg / kg), POSTN KO mice and WT counterparts were subjected to a left flank incision. UUO was performed by complete ligation of the left ureter at the ureteropelvic junction, using double silk sutures. Controlateral kidneys were used as controls. Mice were sacrificed at day 15.

[0093]Animal...

example 2

Periostin Antisens Oligonucleotide Periostin Protect Against the Development of in a Hypertensive Nephropathy Rat Model (L-NAME Treated Rats)

[0119]Material & Methods

[0120]Animals:

[0121]Male Sprague-Dawley rats, weighing 250 g, were maintained on a normal-salt diet and had free access to chow and water. To induce a hypertensive nephropathy model, LNAME, an inhibitor of NO synthesis, was given via drinking water at the dose of 30 mg / kg / day. In order to investigate the role of periostin, the inventors used an antisense approach to down regulate its expression.

[0122]Administration of Antisense (AS) Against Periostin:

[0123]To block periostin expression, the inventors used a specific AS oligodeoxynucleotides (ODN) modified with phosphorothioate to prevent their in vivo hydrolysis by nucleases. The AS or scrambled control ODNs were administrated by intraperitoneal (IP, 1 μM) either in a preventive or curative way. In the preventive protocol, antisense injection started with LNAME administr...

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Abstract

The present invention relates to methods for preventing and treating chronic kidney disease (CKD).

Description

FIELD OF THE INVENTION[0001]The present invention relates to methods for preventing and treating chronic kidney disease (CKD).BACKGROUND OF THE INVENTION[0002]Chronic Kidney Disease (CKD) can result from different causes, but the final pathway remains renal fibrosis characterized by chronic inflammation leading to abnormal accumulation of extracellular matrix (ECM). This fibrotic process leading to a decrease in the number of functioning nephrons is still not clear and constitutes the key of CKD progression. Thus, new insights into the pathophysiological mechanisms of renal fibrogenesis will guide us to a more efficient therapy. The amount of ECM is regulated by the balance between protein synthesis and degradation and it's particularly important during embryonic development and pathological states. While fibrogenesis mechanisms have been the subject of ongoing studies, attention has become focused on ECM proteins, due to their importance not only as components of fibrosis, but also...

Claims

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Application Information

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IPC IPC(8): C12N15/113C12N15/115C07K16/18
CPCC12N15/113C07K16/18C12N15/115C12N2310/315C12N2310/16C12N2310/11C07K2317/76C12N15/1138A61P13/02A61P13/12A61P29/00A61P37/06A61P43/00A61P9/10A61P9/12A61P9/14A61P3/10
Inventor CHATZIANTONIOU, CHRISTOSDUSSOLE, JEAN-CLAUDECONWAY, SIMON J.
Owner INST NAT DE LA SANTE & DE LA RECHERCHE MEDICALE (INSERM)
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