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Use of cgrp receptor antagonists in neuroprotection and neurological disorders

A receptor antagonist, calcitonin technology, used in the treatment of diseases related to high LDL levels, can solve problems such as ganglion cell apoptosis

Inactive Publication Date: 2019-06-21
克里斯托弗·J·索尔斯
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Likewise, genetic mutations and oxidative damage can lead to ganglion cell apoptosis

Method used

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  • Use of cgrp receptor antagonists in neuroprotection and neurological disorders
  • Use of cgrp receptor antagonists in neuroprotection and neurological disorders
  • Use of cgrp receptor antagonists in neuroprotection and neurological disorders

Examples

Experimental program
Comparison scheme
Effect test

Embodiment approach 1

[0232] The effect of a peptide CGRP receptor antagonist (SEQ ID NO: 1 ) on locomotor activity in C-nociceptors in a rat model of nerve injury was assessed.

[0233] To investigate the effect of CGRP receptor antagonists on pathological spontaneous activity in C-nociceptors, the following experiments were performed on Sprague-Dawly rats. Crush-induced sciatica developed in 12 male Sprague-Dawley rats. Spontaneous activity in injured C-nociceptors was then examined using microneurographs and responses to CGRP receptor antagonists were assessed under open-label conditions. This study aimed to evaluate the effect of CGRP receptor antagonists on electrophysiological measures of spontaneous activity in a subpopulation of impaired C-nociceptors in a model of neuropathic pain and to investigate the effect of CGRP receptor antagonists on peripheral C-nociceptors Effects of pathological locomotor activity.

[0234] Materials and methods

[0235] All experiments were performed in ac...

Embodiment approach 2

[0292] Embodiment 2: Use of CGRP Antagonists in Rat Experimental Glaucoma Model

[0293] Ganglion cells of the retina and optic nerve are the main sites of injury in glaucoma. The initial damage can be several possibilities, such as genetic mutation, elevated intraocular pressure, or oxidative damage, all of which can lead to ganglion cell apoptosis, a natural but usually quiescent pathway, When activated, it causes cell death. Diseased, injured or stressed cells essentially "suicide". Vision researchers have now studied many steps in the apoptotic pathway of ganglion cells and can begin testing inhibitors that could block this pathway, thereby at least slowing down ganglion cell dysfunction and death.

[0294] The aim of this study was to investigate the neuroprotective properties of CGRP antagonists in a rat experimental glaucoma model.

[0295] In this study, Wistar rats (n=12) were used for experiments. The neuroprotective properties of the compound were investigated...

Embodiment approach 3

[0335] Embodiment 3. Evaluation of the effect of CGRP receptor antagonist administration on LDL levels in rats

[0336] Familial hypercholesterolemia (FH) is a genetic disorder characterized by high cholesterol levels, especially high levels of low-density lipoprotein (LDL) in the blood and early cardiovascular disease. Individuals with FH may have high cholesterol levels that are less responsive to standard treatments for controlling cholesterol levels. Without limitation, these types of treatments include statins, selective cholesterol absorption inhibitors, resins (bile acid sequestrants or bile acid binders), and lipid-lowering therapy. However, therapy (including higher statin doses) and lifestyle changes are the standard of care for patients with FH.

[0337] Research

[0338] In the course of a routine study of the peptide CGRP antagonist (SEQ ID NO: 1 ) in order to assess the off-target effects of the compound, it was found that the test compound favorably reduce...

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PUM

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Abstract

Provided herein are treatment methods, including methods of treating nerve damage, methods of neuroprotection, methods of treating glaucoma and methods of lowering LDL levels. The methods generally involve administering to an individual in need thereof an effective amount of a CGRP receptor antagonist peptide or composition.

Description

[0001] Incorporation by reference of any priority application [0002] This application claims the benefit of U.S. Provisional Application No. 62 / 383,334, filed September 2, 2016, which is hereby incorporated by reference in its entirety. [0003] References to Sequence Listings, Tables, Computer Program Listings [0004] This application is filed together with a Sequence Listing in electronic format. The Sequence Listing is provided as a file named CSOAR.003WO.TXT created on August 30, 2017, which is 15.9 kb in size. This information is in electronic format of the Sequence Listing, the entire contents of which are incorporated herein by reference. technical field [0005] This embodiment relates to the therapeutic use of antagonists of the calcitonin gene-related peptide (CGRP) receptor for neuroprotection and treatment of acute and chronic diseases and disorders associated with neurodegeneration, including, for example, the treatment of glaucoma. Additionally, provided he...

Claims

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Application Information

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IPC IPC(8): A61K38/17A61P25/00A61P27/06
CPCA61K38/1709A61P21/00A61P25/00A61P25/02A61P25/04A61P25/14A61P25/16A61P25/28A61P27/06A61P29/00A61P3/06A61P39/02A61P43/00A61P9/10Y02A50/30C07K14/57527C07K14/435A61K38/00
Inventor 克里斯托弗·J·索尔斯
Owner 克里斯托弗·J·索尔斯
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