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Sobetirome in the treatment of myelination diseases

A disease and myelin technology, which is applied in the field of sobuterosol for the treatment of myelination diseases, which can solve the problems of no effective treatment and other problems

Inactive Publication Date: 2016-03-23
OREGON HEALTH & SCI UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

For some demyelinating diseases, there are no known effective treatments

Method used

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  • Sobetirome in the treatment of myelination diseases
  • Sobetirome in the treatment of myelination diseases
  • Sobetirome in the treatment of myelination diseases

Examples

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Effect test

Embodiment 1

[0137] Embodiment 1: Sobutirol is used for the purposes of treating multiple sclerosis (MS)

[0138] This example describes the discovery that treatment with sobutirol reduces demyelination in two different animal models of MS.

[0139] Chronic demyelination contributes to disability and progressive damage in MS

[0140] In MS, inflammatory cells induce multifocal demyelination and variable axonal degeneration in the CNS, termed MS plaques. As a result, individuals with MS develop a variety of neurological deficits, including paralysis, gait impairment, cognitive impairment, sensory loss, and decreased vision. Although remyelination occurs spontaneously in MS as part of the natural repair process, it is incomplete and tends to become ineffective as the disease progresses. Failure of remyelination results in chronically demyelinated axons that lose their ability to normally conduct axons, leading to neurological dysfunction. Importantly, chronic demyelination contributes to ...

Embodiment 2

[0153] Example 2: Sobutirol in an animal model of neonatal hypoxia

[0154] Chronic neonatal hypoxia is a clinically relevant model of preterm brain injury caused by insufficient gas exchange due to lung hypoplasia. This hypoxic state is a significant contributor to the diffuse white matter injury (DWMI) commonly seen in preterm infants. Chronic hypoxia can cause abnormal myelination. A mouse model of chronic hypoxia has been described previously (Scafidi et al., Nature doi: 10.1038 / naturel2880 [epub ahead of publication], 5 December 2013). This model can be used to evaluate the effect of sobutirol on oligodendrocyte regeneration and remyelination after hypoxia.

[0155] Mice were randomly selected to undergo hypoxic feeding or serve as normoxic controls. Hypoxic mice were placed in a sealed chamber, as previously described, by dosing with N 2 Replace O 2 The concentration was maintained at 10.5% (Raymond et al., JNeurosci 31:17864-17871, 2011; Bi et al., JNeurosci 31:920...

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Abstract

Methods of treating a subject having or at risk of developing a neurodegenerative disease or condition associated with demyelination, insufficient myelination, or underdevelopment of myelin sheath are described. The methods include administration of a therapeutically effective amount of sobetirome, or a pharmaceutically acceptable salt thereof.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to International Application PCT / US2013 / 053640, filed August 5, 2013, and to U.S. Provisional Application 61 / 819,467, filed May 3, 2013, the publications of each of which The contents are all incorporated herein by reference. technical field [0003] The present disclosure relates to methods for treating diseases or conditions associated with demyelination, hypomyelination, or myelin hypoplasia. The present disclosure also relates to the use of sobetirome for the treatment of such diseases and conditions. [0004] Confirmation of government support [0005] This invention was made with government support under Grant No. DK-52798 awarded by the National Institutes of Health. The government has certain rights in this invention. [0006] Parties to a joint research agreement [0007] The invention described in this application was made by Oregon Health & Sciences University and the Unit...

Claims

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Application Information

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IPC IPC(8): A61K38/24A61P25/00A61P25/28C07C59/48
CPCA61K9/0095A61K31/192A61P1/00A61P13/12A61P15/10A61P21/00A61P25/00A61P25/02A61P25/14A61P25/28A61P27/00A61P27/16A61P5/00A61P5/14A61P5/38A61P5/40A61K9/0053
Inventor 托马斯·S·斯坎伦梅雷迪思·哈特利安德鲁·普拉切克马可·瑞纪丹尼斯·布尔德特盖尔·卡拉齐普利亚·乔杜里
Owner OREGON HEALTH & SCI UNIV
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