Methods for treating inflammation

a technology of inflammation and treatment, applied in the field of inflammation treatment, can solve the problems of impaired glucose-induced insulin secretion from the pancreatic islets, glucose tolerance defect when challenged, impaired chylomicron remnant clearance, etc., and achieve normal response level, reduced basal expression, and reduced inhibition

Active Publication Date: 2012-07-19
ENZO BIOCHEM
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0014]The present invention discloses the identification and use of molecules that bind to members of the LRP family thereby providing for relief in subjects suffering from inflammation, an immune mediated disorder, a metabolic disorder, a pathological condition associated with an elevation of TNF-α, a pathological condition associated with elevation of mmp, a skin condition or disease, an organ or tissue injury or any combination of the foregoing. Other molecules that may be of use in the present invention may bind to a factor that interacts with an LRP thereby preventing its binding to LRP, where the disruption of this binding may also provide relief from the foregoing conditions.

Problems solved by technology

Although fasted blood glucose and insulin levels were normal in the mutant strains, they showed a defect in glucose tolerance when challenged.
These animals also showed impaired clearance of chylomicron remnants and also impaired glucose-induced insulin secretion from the pancreatic islets.
On the other hand, for multi-ligand signal receptors, another layer of complexity is observed where different domains participate in different reactions.
Not surprisingly, further experiments showed a lack of stimulation when Wnt was added.
However, in this group of compounds (Group 2), the addition of Wnt showed no stimulation, indicating an inability to respond to Wnt in the presence of these compounds.

Method used

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  • Methods for treating inflammation
  • Methods for treating inflammation
  • Methods for treating inflammation

Examples

Experimental program
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Effect test

example 1

[0055]Effects of Gallic Acid and Digallic Acid on Wnt and Dkk Suppression of Wnt.

[0056]This experiment was carried out as previously described in U.S. Patent Application No. 20050196349 using Gallic Acid, a small molecule that represents a partial constituent of the IIIC3 molecule as well as Digallic Acid, which represents a dimeric form of Gallic Acid. The structures of Gallic Acid and Digallic Acid are provided below:

[0057]As seen in FIG. 2A, the small molecule derivative of IIIC3 is capable of providing protection against Dkk suppression when present at 30 mM. In this experiment, the Digallic Acid completely blocked Dkk at even the lowest (1.2 mM) value tested.

example 2

[0058]Effects of Digallic Acid on Wnt and Dkk Suppression of Wnt.

[0059]This experiment was carried out as described above except that a lower range of drug dosage was used as compared to Example 1. In FIG. 3A, there is essentially no effect upon either Wnt activity or suppression of Wnt activity by Dkk when up to 3.3 mM Gallic Acid was present (similar to what was seen with Example 1, FIG. 2A). In contrast, FIG. 3B shows that modest effects upon Wnt activity at the higher (1.1 and 3.3 uM) dosages and a dose dependent effect upon inhibition of Dkk suppression showing that the dimeric form is much more potent than the monomeric form. Both FIGS. 2 and 3 indicate that nearly 30 times as much Gallic Acid had to be present to achieve the same effect as the dimeric Gallic Acid.

example 3

[0060]Stimulatory Effects of Enzo IIC8 on Alveolar New Bone Formation in a Tooth Extraction Model.

[0061]A root extraction model (Lin et al., 1994 Anat Record 240; 492-506) was used to determine whether IIC8 (described in U.S. Patent Application No. 20050196349) is able to stimulate new bone formation. The bone regeneration process following tooth extraction is a complex phenomenon that involves wound healing, as well as bone formation. Briefly, the initial coagulum is followed by the formation of woven bone, lamellar bone, bone marrow, and cortical bone. At the cellular level this process involves induction and regulation of growth of several distinct cell types, as well as differentiation of stem cells into several cell types. The point of the experiment described below was to determine whether a drug could accelerate the process of bone growth without adversely affecting the end product of the process.

[0062]Procedure: 10 week old Sprague Dawley rats (˜300 gram body weight obtained...

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Abstract

The present invention relates to the field of therapeutic methods, compositions and uses thereof, that affect, directly or indirectly, the behavior of LRP receptors. These compositions and methods result in the treatment of inflammatory, immunological and metabolic conditions. More particularly, the methods and compositions of the invention are directed to the identification of small molecules, drugs and / or pharmacological agents that affect the Wnt pathway by affecting normal complex formation among various signaling receptors, the LRP5 and LRP6 receptor, and related ligands.

Description

REFERENCE TO RELATED PATENT APPLICATIONS[0001]This application claims the benefit of U.S. Provisional Patent Application No. 60 / 963,774, filed on Aug. 7, 2007, entitled “Compositions and Methods Affecting the Signaling Pathways of LRP Receptors” the contents of which are incorporated herein by reference.[0002]This application is related to the patent application entitled “Compositions and Methods for the Stimulation or Enhancement of Bone Formation and the Self-Renewal of Cells”, by Dan Wu, et al. filed on May 19, 2004, and its entire contents is hereby incorporated by reference, in its entirety.[0003]This application is a Continuation-in-Part of application Ser. No. 11 / 591,153 filed Nov. 1, 2006, which is a Continuation-in-Part of application Ser. No. 11 / 097,518 filed Apr. 1, 2005, which is a Continuation-in-Part of application Ser. No. 11 / 084,668 filed Mar. 18, 2005, which is Continuation-in-Part of application Ser. No. 10 / 849,067, filed May 19, 2004, which claims the benefit of U...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/235A61P29/00A61P37/02A61P3/08C40B30/04A61K31/192A61K31/185C40B30/06C40B30/02A61P3/06A61P17/14
CPCA61K38/00G01N33/5011G01N33/5041G01N33/564A61K31/395G01N2333/705G01N2800/24A61K31/535A61K31/015G01N33/92A61K31/185A61K31/192A61K31/235A61K31/538A61P3/10
Inventor RABBANI, ELAZARLI, XIAOFENGLIU, DAKAIZHANG, YAZHOUJIN, RICHARDBHATTACHARYYA, RIDDHICHENG, WEIDONEGAN, JAMES J.
Owner ENZO BIOCHEM
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