Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Compounds and methods for the treatment of autoimmune and inflammatory disease

A technology for autoimmunity and diseases, applied in allergic diseases, metabolic diseases, skin diseases, etc.

Inactive Publication Date: 2012-01-04
都柏林伊丽莎白女皇神学院院长、研究员及专家协会
View PDF2 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although there is still some debate in the literature, it is very likely that Th1 and Th17 cells cooperate to induce the development of organ-specific autoimmunity

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Compounds and methods for the treatment of autoimmune and inflammatory disease
  • Compounds and methods for the treatment of autoimmune and inflammatory disease
  • Compounds and methods for the treatment of autoimmune and inflammatory disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0137] Example 1 - Treatment with the NOD1 agonist Tri-DAP attenuates experimental autoimmune cerebrospinal inflammation (EAE)

[0138] This assay was designed to identify whether Tri-DAP therapy was able to reduce clinical scores of disease severity following induction of EAE in mice.

[0139] Materials and methods:

[0140] On day 0, C57BL / 6 mice were injected subcutaneously (s.c.) with 150 μg MOG 35-55 Induced EAE, MOG 35-55 Present in CFA supplemented with 4 mg / ml H37Ra M. tuberculosis. On days 0 and 2, all mice were injected intraperitoneally (i.p.) with pertussis toxin (PT). One group of mice received no treatment and a second group was given Tri-DAP (100 μg / mouse) in MOG / CFA emulsion on day 0 and again on day 1, day 2 and every two days thereafter. Clinical scores were assessed daily and body weights were recorded. Disease severity was graded as follows: Grade 0: normal; Grade 1: tail lameness; Grade 2: gait wagging; Grade 3: hindlimb weakness; Grade 4: hindl...

Embodiment 2-E

[0144] Example 2 - Treatment with NOD1 agonist Tri-DAP following EAE induction inhibits MOG specificity inflammatory cytokines

[0145] The assay was designed to determine the effect of Tri-DAP treatment on Th1 and Th17 specific inflammatory cytokine production after EAE induction.

[0146] Materials and methods:

[0147] On day 0, C57BL / 6 mice were injected subcutaneously with 150 μg MOG 35-55 Induced EAE, MOG 35-55 Present in CFA supplemented with 4 mg / ml H37Ra M. tuberculosis. On days 0 and 2, all mice were injected intraperitoneally with PT. One group of mice received no treatment, the second group was given 100 μg Tri-DAP 6 hours before immunization, the third group was given Tri-DAP (100 μg / mouse) with MOG / CFA emulsion on the 0th day, and on the 1st, 2nd day And 4 days to give again. Mice were sacrificed on day 5 and lymph node cells were stimulated with MOG peptide (myelin oligodendrocyte glycoprotein) (20-100 μg / ml) or medium alone or PMA and anti-CD3 as neg...

Embodiment 3

[0151] Example 3 - In the brain of mice with EAE, the use of NOD1 agonist Tri-DAP to treat inhibitory T cells expressing IL-17 and expressing IFNγ

[0152] The assay was designed to determine the effect of Tri-DAP treatment on various IFN-γ and IL-17 producing T cell populations in the mouse brain following EAE induction.

[0153] Materials and methods:

[0154] Twelve days after EAE induction, monocytes were isolated from the brains of control EAE or Tri-DAP-treated EAE mice. Cells were restimulated overnight with PMA / ionomycin and incubated with brefeldin A. With anti-CD3 ( Figure 4 ), or anti-CD3 and anti-CD4 ( Figure 5 and 6 ) to stain the cells. Cells were then fixed and permeabilized, stained intracellularly with anti-IFN-γ and anti-IL-17, and analyzed by flow cytometry.

[0155] result:

[0156] In all tested T cell populations ( Figure 4 CD3 + cell, Figure 5 CD3 + CD4 + cells and Figure 6 CD3 + CD4 - cells), Tri-DAP treatment inhibited the p...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
molecular weightaaaaaaaaaa
Login to View More

Abstract

The present invention provides a method and composition for the treatment and prevention of an autoimmune disease such a multiple sclerosis which is mediated by autoreactive T cells. The administration of a NOD-1 agonist is shown to mediate an anti-inflammatory immune response. NOD-1 agonists suitable for use in the methods and compositions of the invention include diaminopimelic acid (DAP)-containing muropeptide compounds such as Tri-DAP and M-TriDAP.

Description

technical field [0001] The present invention relates to compositions and methods for the treatment and prevention of disease conditions mediated by T-helper 17 (Th17) and / or T-helper 1 (Th1) T lymphocytes (T cells). In particular, the present invention relates to the use of diaminopimelic acid (DAP) containing muramide compounds for the treatment of disease conditions mediated by autoreactive Th17 and Th1 T lymphocytes. The compounds and methods of the invention are also useful in methods of modulating an immune response by inhibiting the cytokines interleukin 17 (IL-17), interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-α) production, while enhancing the expression of IL-27, IL-10 and IL-35. Background technique [0002] Protective immunity against specific diseases relies on the differential induction of specific proinflammatory T cell (T lymphocyte) populations by antigen presenting cells (APCs) of the innate immune system, such as dendritic cells (DCs) a...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/14A61P37/06A61P17/06A61P25/00A61P19/02
CPCA61K38/14A61P1/00A61P1/04A61P17/06A61P19/02A61P25/00A61P29/00A61P37/02A61P37/06A61P43/00A61P3/10
Inventor 金斯敦·米尔斯莎拉·希金斯
Owner 都柏林伊丽莎白女皇神学院院长、研究员及专家协会
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com