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A kind of pharmaceutical composition for treating multiple sclerosis

A multiple sclerosis and composition technology, applied in the field of biomedicine, can solve the problems of not being able to reduce the number of plasma cells and self-reactive memory B cells, repeated and exacerbated MS conditions, etc., to reduce the level, reduce the reaction of autoantigens, The effect of reducing the number

Inactive Publication Date: 2016-08-03
INST OF BASIC MEDICAL SCI ACAD OF MILITARY MEDICAL SCI OF PLA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the method of blocking BAFF therapy also has certain defects. In the brains of MS patients, there are lymphoid follicle structures in which B cells can continuously expand and differentiate into plasma cells or self-reactive memory B cells. MS relapses and worsens by releasing autoantibodies or acting as antigen-presenting cells
Although anti-BAFF antibody alone can significantly reduce the number of mature B cells in peripheral blood, it cannot reduce the number of plasma cells and self-reactive memory B cells [VincentFB, et al. BAFF and innate immunity: new therapeutic targets for systemiclupuserythematossu. ImmunolCellBiol.

Method used

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  • A kind of pharmaceutical composition for treating multiple sclerosis
  • A kind of pharmaceutical composition for treating multiple sclerosis
  • A kind of pharmaceutical composition for treating multiple sclerosis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Example 1 Effect of TACI-IgG and Anti-IL-15 Antibody Combined Therapy on B Cells

[0032] 1. Materials and methods

[0033] 1. Materials

[0034] BALB / c mice were purchased from the Animal Center of the Academy of Military Medical Sciences; mouse myelin oligodendrocyte glycoprotein 33-55 (MOG33-55), complete Freund's adjuvant (CFA), and pertussis toxin were purchased from Sigma; rabbits Anti-mouse B220 monoclonal antibody, rabbit anti-mouse CD3 monoclonal antibody, rabbit anti-mouse CD21 monoclonal antibody, rabbit anti-mouse CD23 monoclonal antibody were purchased from Abcam; BAFF inhibitor TACI-IgG, anti-mouse IL-15 neutralizing antibody were purchased from R&D company.

[0035] 2. Method

[0036] 2.1. Construction of EAE mouse model

[0037] Dilute MOG35-55 to 2mg / mL with 0.01mol / L PBS, then fully mix the diluted solution with an equal amount of complete Freund’s adjuvant, and pump the emulsion into a water-in-oil state through a three-way tube, which is to induc...

Embodiment 2

[0060] Example 2 Effect of TACI-IgG and Anti-IL-15 Antibody Combined Therapy on Helper T Cells (Th1, Th17)

[0061] 1. Materials and methods

[0062] 1. Materials

[0063] BALB / c mice were purchased from the Animal Center of the Academy of Military Medical Sciences; mouse myelin oligodendrocyte glycoprotein 33-55 (MOG33-55), complete Freund's adjuvant (CFA), and pertussis toxin were purchased from Sigma; rabbits Anti-mouse CD4 monoclonal antibody, rabbit anti-mouse IL-17 monoclonal antibody, rabbit anti-mouse IFNγ monoclonal antibody were purchased from Abcam; BAFF inhibitor TACI-IgG, anti-mouse IL-15 neutralizing antibody were purchased from R&D Company.

[0064] 2. Method

[0065] 2.1. Construction of EAE mouse model

[0066] Dilute MOG35-55 to 2mg / mL with 0.01mol / L PBS, then fully mix the diluted solution with an equal amount of complete Freund’s adjuvant, and pump the emulsion into a water-in-oil state through a three-way tube, which is to induce EAE antigenic emulsion...

Embodiment 3

[0088] Example 3 Effect of TACI-IgG and Anti-IL-15 Antibody Combined Therapy on Memory T / B Cells

[0089] 1. Materials and methods

[0090] 1. Materials

[0091] BALB / c mice were purchased from the Animal Center of the Academy of Military Medical Sciences; mouse myelin oligodendrocyte glycoprotein 33-55 (MOG33-55), complete Freund's adjuvant (CFA), and pertussis toxin were purchased from Sigma; rabbits Anti-mouse B220 monoclonal antibody, rabbit anti-mouse CD44 monoclonal antibody, rabbit anti-mouse CD27 monoclonal antibody, rabbit anti-mouse CD3 monoclonal antibody were purchased from Abcam; BAFF inhibitor TACI-IgG, anti-mouse IL-15 neutralizing antibody were purchased from R&D company.

[0092] 2. Method

[0093] 2.1. Construction of EAE mouse model

[0094] Dilute MOG35-55 to 2mg / mL with 0.01mol / L PBS, then fully mix the diluted solution with an equal amount of complete Freund’s adjuvant, and pump the emulsion into a water-in-oil state through a three-way tube, which is...

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PUM

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Abstract

The invention discloses a medicinal composition for treating multiple sclerosis, and the medicinal composition comprises BAFF (B cell activating factor belonging to TNF family) inhibitor (TACI-IgG) and IL-15 inhibitor (anti IL-15 antibody). The medicinal composition is used for treating a murine model EAE (experimental allergic encephalomyelitis) mice subjected to the multiple sclerosis, and the results showed that the medicinal composition can significantly reduce the number of B cells, helper T cells and memory B / T cells in spleen and lymph nodes, inhibits the production of activation and autoimmune antibodies of the B cells, and relieves clinical autoimmune symptoms. The medicinal composition is effective in the treatment of the multiple sclerosis.

Description

technical field [0001] The invention belongs to the field of biomedicine and relates to a pharmaceutical composition for treating autoimmune disease multiple sclerosis (MS). Specifically, the composition of the present invention includes a BAFF inhibitor and an IL-15 inhibitor, and animal experiments show that the pharmaceutical composition can effectively inhibit the occurrence and development of autoimmunity. Background technique [0002] With the development of social times, the incidence of autoimmune diseases in various groups of people in our country has been increasing. In view of the fact that the late stage of the disease will cause serious harm to people's life, work and even their own health in the future, further strengthening the basic research on autoimmune diseases will help humans understand the mechanism of the occurrence, development and prognosis of such diseases, Thereby improving the level of its prevention, diagnosis and treatment. This has important ...

Claims

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Application Information

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IPC IPC(8): A61K39/395A61P37/02A61P25/28A61P3/10
Inventor 王仁喜黎燕肖鹤韩根成陈国江侯春梅沈倍奋马宁邢陈
Owner INST OF BASIC MEDICAL SCI ACAD OF MILITARY MEDICAL SCI OF PLA
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