Unlock instant, AI-driven research and patent intelligence for your innovation.

Compositions and methods for detecting and treating pathological fibroblast cells

a technology of pathological fibroblasts and compositions, applied in the field of compositions and methods for detecting and treating pathological fibroblasts, can solve the problems of lack of current existence, loss of function, organ failure, etc., and achieve the effect of reducing the number of pathologic myofibroblast subpopulations, rapid elimination of this pathologic myofibroblast subpopulation, and inducing cell death

Inactive Publication Date: 2020-10-08
DUKE UNIV
View PDF0 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention is about a new method to diagnose and treat fibrotic diseases in humans. The inventors found that a specific protein called pro-N-cadherin is present on a small group of fibroblasts that cause damage to tissues. This protein can be targeted with a special antibody, which then kills these harmful fibroblasts without affecting other healthy cells. This technique may be useful for identifying and treating fibrotic diseases in the heart, lung, and liver.

Problems solved by technology

Fibrosis is the aberrant remodeling of tissue architecture which results in loss of function and inevitably organ failure.
However, a true disease specific marker for these cells does not currently exist.

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
  • Compositions and methods for detecting and treating pathological fibroblast cells
  • Compositions and methods for detecting and treating pathological fibroblast cells
  • Compositions and methods for detecting and treating pathological fibroblast cells

Examples

Experimental program
Comparison scheme
Effect test

examples

[0237]The following examples are illustrative, but not limiting, of the compounds, compositions, and methods of the present invention. Other suitable modifications and adaptations of the variety of conditions and parameters normally encountered in clinical therapy and which are obvious to those skilled in the art are within the spirit and scope of the invention.

example i

[0238]This example describes the expression of Pro-N-cadherin on the cell surface of fibroblasts isolated from tissues pathological in origin but not expressed on the cell surface of fibroblasts isolated from non-diseased tissues.

[0239]A murine monoclonal antibody (mAb) was obtained from the University of Nebraska Medical School. This antibody is highly specific for the precursor (pro) domain of Pro-N-cadherin (see, Wahl, J. K., et al Journal of Biological Chemistry, 2003. 278(19): p. 17269-17276). Western blot analysis shows that this mAb recognizes Pro-N-cadherin protein from human pathological fibroblasts from lung (LL97A), heart (CF-DCM) and liver (LX2) with no protein expression detected in normal fibroblasts NHLF and CCD-16lu (FIG. 1B) due to normal N-cadherin protein processing. Aberrant cell surface localization of Pro-N-cadherin is demonstrated by flow cytometry analyzed pathological fibroblasts from lung (LL97A), heart (CF-DCM) and liver (LX2) with no cell surface localiza...

example ii

[0240]This example demonstrates that mAb treatment targeting the pro-domain of the precursor N-cadherin results in reduction of proliferation, activation and viability of pathological fibroblasts. This example also demonstrates the phenomenon defined as the hook effect (Also known as the prozone effect) related to monoclonal antibodies.

[0241]To assess whether administering an antibody against the Pro-N-cadherin protein can result in cell death, LL97A diseased fibroblasts were treated monoclonal antibody (10A10), that specifically targets the pro domain of the precursor N-cadherin molecule. Administration of the 10A10 antibody resulted in cell death of approximately seventy-five percent of the fibroblast population overnight, confirmed by trypan blue staining (FIG. 2). FIG. 2 demonstrates reduced viability of pathological LL97A fibroblasts with Pro-N-cadherin treatment. Pathological fibroblasts from heart, lung and liver were challenged with Pro-N-cadherin mAb and effects were measur...

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
dissociation constantaaaaaaaaaa
dissociation constantaaaaaaaaaa
dissociation constantaaaaaaaaaa
Login to View More

Abstract

Compositions, kits and methods for assessing the presence of pathological fibroblasts within a biological sample are provided. In addition, compositions, kits and methods for detecting fibrosis are provided. Also provided are methods for treating fibrosis and conditions characterized with pathological fibroblasts.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]The present application is a continuation of U.S. patent application Ser. No. 16 / 586,532, filed Sep. 27, 2019, which claims priority to Mexican Patent Application No. 62 / 737,167, filed on Sep. 27, 2018, the entire contents of all of which are fully incorporated herein by reference.FIELD OF THE INVENTION[0002]Compositions, kits and methods for assessing the presence of pathological fibroblasts within a biological sample are provided. In addition, compositions, kits and methods for detecting fibrosis are provided. Also provided are methods for treating fibrosis and conditions characterized with pathological fibroblasts.INTRODUCTION[0003]Fibrosis is the formation of excess fibrous tissue in an organ or tissue, often as a reaction to inflammation or tissue injury. Pathological fibrosis is characterized by non-resolving or progressive tissue remodeling, which itself can cause tissue damage and organ failure.[0004]Pathological fibroblasts are t...

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(United States)
IPC IPC(8): G01N33/50C12Q1/6881C07K16/28A61K39/395A61P11/00A61K45/06
CPCA61K39/3955G01N2800/12C12Q2600/158A61P11/00G01N33/5091C12Q1/6881C07K16/2896A61K45/06G01N2800/10C07K2317/73C12Q1/6883G01N33/56966G01N2333/705G01N2800/085
Inventor FERRELL, PAULPIZZO, SALVATOREBACHELDER, ROBIN
Owner DUKE UNIV