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Application of targeting optineurin in the preparation of drugs for the prevention and treatment of autoimmune diseases

An autoimmune, drug-based technology that can be used in medicine to solve problems such as death and disability

Active Publication Date: 2020-10-27
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

These diseases are often chronic and persistent, and there are no effective preventive and therapeutic drugs in clinical practice, which eventually lead to disability or death

Method used

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  • Application of targeting optineurin in the preparation of drugs for the prevention and treatment of autoimmune diseases
  • Application of targeting optineurin in the preparation of drugs for the prevention and treatment of autoimmune diseases
  • Application of targeting optineurin in the preparation of drugs for the prevention and treatment of autoimmune diseases

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Peripheral blood samples were collected from 30 cases of MS and RA respectively. Peripheral blood mononuclear cells (PBMC) were obtained by Ficoll gradient separation, and the mRNA level of Optn was detected by qRT-PCR. see figure 1 , the mRNA level of Optn in PBMC of MS and RA patients was higher than that of healthy controls (Healthy Donor, HD).

Embodiment 2

[0027] Using WT and Optn - / - The EAE model was established in C57BL / 6 adult female mice. The specific EAE modeling method is as follows: MOG 35-55 It was dissolved in sterile PBS and mixed with complete Freund's adjuvant containing Mycobacterium tuberculosis to prepare an emulsion. The emulsion was subcutaneously injected into the neck of the mice and the left and right hind limbs of the mice, and pertussis toxin was injected into the tail vein at the same time. On the second day after modeling, pertussis toxin was injected into the tail vein again. The scoring criteria of EAE simulated clinical multiple sclerosis symptoms were as follows: 0 points, no symptoms; 1 point, tail weakness; 2 points, tail weakness and partial limb weakness; 3 points, paralysis of one hind limb; 4 points, paralysis of both hind limbs; 5 points, moribund or dead. From the day of modeling (denoted as Day 0), EAE symptoms were scored every day. And at the end of the disease, the mouse spinal cord ...

Embodiment 3

[0030] Extract WT and Optn - / - Bone marrow-derived dendritic cells (BMDC) of mice were given LPS, and the cells were harvested 24 hours later for co-staining with CD11C and CD80, and MHC I or MHC II was used to detect the maturation of dendritic cells. see image 3 A-C, Knockdown of Optn inhibits dendritic cell maturation.

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Abstract

The invention provides application of Optineurin as a target point in the preparation of a drug for preventing and treating autoimmune diseases. The drug comprises an antibody specifically combined with an OPTN protein, an Optineurin gene-specific siRNA, an sh-OPTN adeno-associated disease, and an Optineurin small-molecule inhibitor of a steroid derivative shown in the formula (I). The study of the application demonstrates that by inhibiting the Optn gene expression, the maturation of dendritic cells can be inhibited, the polarization of CD4<+>T cells to Th2 and Treg for inflammation suppression is promoted, and the polarization of the CD4<+>T cells to Th1 and Th17 for inflammation promotion is inhibited, so that the autoimmunization system is inhibited, and the effect of treating autoimmune diseases such as multiple sclerosis and rheumatoid arthritis is achieved. The invention discloses a novel role of the Optn gene in immune cells and immune systems, the design and preparation of thedrug for preventing and / or treating the autoimmune diseases by using the Optn gene or protein as the target point and other therapeutic means.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to the application of Optineurin as a target in the preparation of drugs for the prevention and treatment of autoimmune diseases. Background technique [0002] Optineurin (OPTN), encoded by the Optn gene, is mainly involved in autophagy as an autophagy receptor. At present, the function of this protein has not been fully elucidated. Studies have reported that it is closely related to amyotrophic lateral sclerosis and primary open-angle glaucoma; in terms of immunity, it has been reported that the Optn gene has a positive effect on patients with Crohn's enteritis and Paget's disease of bone. Abnormal expression in the medium may be involved in the occurrence and development of immune diseases. Autoimmune diseases are diseases caused by the immune system's immune response to the body's own components. The main pathological process is: activated dendritic cells secrete inflammatory f...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K45/00A61K31/713A61K31/58A61P37/02
CPCA61K31/58A61K31/713A61K45/00A61P37/02
Inventor 翁勤洁王佳颖赵梦婷杨丽君杨波何俏军
Owner ZHEJIANG UNIV
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