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Materials and methods for treating chronic fibrotic disease

一种纤维化疾病、纤维化的技术，应用在性疾病、过敏性疾病、化学仪器和方法等方向，能够解决具体作用不明确等问题

Inactive Publication Date: 2009-01-21
RGT UNIV OF MICHIGAN
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] In pulmonary fibrosis, chemokines are involved in the formation of fibroblast foci and the amplification of the fibrotic response. The specific role of the pro-fibrotic mediator environment during chronic pulmonary fibrosis is unclear

Method used

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  • Materials and methods for treating chronic fibrotic disease
  • Materials and methods for treating chronic fibrotic disease
  • Materials and methods for treating chronic fibrotic disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0100] Example 1: Methods and materials for demonstrating the role of CCR7 in idiopathic interstitial pneumonia

[0101] Patients suspected of having IIP were identified based on a compilation of clinical, physiologic, radiographic, and pathological findings (Flaherty et al., Am. J. Med., 110:278-282 (2001); Flaherty et al., Curr. OpirPulm. Med., 6: 404-410 (2000); Kazerooni et al., AJR Am. J. Roentgenol. 169: 977-983 (1997); American Thoracic Society, European Respiratory Society (ATS / ERS), Am.J.Respir.Crit.Care Med., 165:277-304(2002)). Prior to this, none of the patients enrolled in this study had undergone biopsy or received IIP treatment. From May 2000 to August 2004 SLBs were performed in April as part of the evaluation of the pathobiology of fibrotic lung disease at the University of Michigan Specialized Center of Research. Distal margins (distant margins) obtained histologically normal lung biopsies without pathological signs of disease. Individual SLBs were processed...

Embodiment 2

[0106] Example 2: Results showing the role of CCR7 in idiopathic interstitial pneumonia

[0107] SuperArray analysis of CCR7, CXCR4, CCL19, CCL21 and CXCL12 transcripts in IIP and normal marginal SLBs. The presence of CCR7 and CXCR4 in IIP and normal marginal SLBs was analyzed with a specific SuperArray GEArray. Although this is a qualitative rather than quantitative technique, the expression of CCR7 (Figure IA) and CXCR4 (Figure IB) can be normalized to the expression of GAPGH, and the values ​​for these two receptors are shown. The highest relative Expression was seen in upper and lower lobe biopsies from UIP patient group (n=7). For tumor patients from NSIP patient group (n=6), RBILD patient group (n=6) and normal margin (n=5) Similar analyzes were performed on lower and upper lobe biopsies. Although no significant differences were detected, overall the relative expression of the two chemokine receptors followed the following disease severity pattern: UIP, NSIP, RBILD, nor...

Embodiment 3

[0124] Example 3: Targeting (targeting) CCL19 or CCL21 for the treatment of chronic fibrotic diseases

[0125] This example illustrates novel potential approaches to target CCL19 and / or CCL21 during chronic fibrosis of the lung. Idiopathic chronic pulmonary fibrosis is known to be very clinically challenging and various treatment options have shown limited efficacy or toxicity (Flaherty et al., Am. J. Med., 110:278-282 (2001) ; (Hampton et al., Am.J.Respir.Crit.Care Med., 149:A878(1994)), the median survival rate after diagnosis hardly changed (Ryu et al., Mayo Clin.Proc., 73 : 1085-1101 (1998); Lasky et al., Environ. Health Perspect., 108 Suppl 4: 751-762 (2000)). Known pro-fibrotic stimuli include radiation, inhaled mineral and organic particles, gaseous oxidants , drugs, and infectious microorganisms, however, the identification of causative factors for the clinicopathological entity that triggers idiopathic interstitial pneumonia (IIP) has been controversial. related, wh...

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Abstract

Methods and compositions for the treatment of fibrosing diseases are described. More specifically, the invention demonstrates that inhibiting or otherwise decreasing the activity of CCL21 either alone or in combination with CCLl9 will be effective in reducing the presence of fibrotic lesions and ameliorating the symptoms of fibrosing disorders.

Description

[0001] This application claims priority to U.S. Provisional Application 60 / 753,647, filed December 23, 2005, which is specifically incorporated herein by reference in its entirety. [0002] This invention was made with government support from the National Institutes of Health under grant number P50 HL-56402. The Government has certain rights in this invention. field of invention [0003] The present invention relates to methods and compositions for the treatment of chronic fibrotic diseases. The present invention relates more particularly to immunotherapeutic intervention in chronic fibrotic diseases. Background of the invention [0004] Inflammation is a coordinated response to tissue injury or infection. When inflammation occurs, it is firstly the local release of chemokines, activation of platelets, coagulation and initiation of complement bypass, which stimulates the local endothelium, causing neutrophils and monocytes to Extravasation of cells. The second stage of inf...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N5/06C12N5/16C12Q1/68C12N15/113
CPCC07K16/2866C12N2310/14C12N15/1138C07K16/24A61K2039/505C07K2316/96C07K2317/76A61P1/16A61P1/18A61P11/00A61P11/08A61P13/12A61P15/00A61P17/00A61P17/02A61P19/02A61P19/04A61P27/02A61P27/06A61P29/00A61P31/04A61P31/22A61P33/12A61P37/06A61P41/00A61P43/00A61P9/04A61P9/10A61P9/12Y02A50/30A61K39/395C12N5/16C12Q1/68C12Q2525/207
Inventor C·M·霍加博亚姆S·L·昆克尔
Owner RGT UNIV OF MICHIGAN
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