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促进少突胶质前体细胞分化和髓鞘再生以治疗多发性硬化症的 13 种化合物:WO2010054307。

Thirteen compounds promoting oligodendrocyte progenitor cell differentiation and remyelination for treating multiple sclerosis: WO2010054307.

机构信息

Dublin City University, School of Biotechnology, Glasnevin, Dublin 9, Ireland.

出版信息

Expert Opin Ther Pat. 2010 Dec;20(12):1767-73. doi: 10.1517/13543776.2010.528393. Epub 2010 Oct 18.

Abstract

BACKGROUND

The application is in the field of cellular therapy and neural repair.

OBJECTIVE

It aims at identifying and characterizing compounds and molecules that promote the differentiation of oligodendrocyte progenitor cells and remyelination of the nervous system.

METHODS

Library of compounds and molecules were screened on a series of assays specifically designed and developed to assess the activity and potency of compounds and molecules on the differentiation of oligodendrocyte progenitor cells and on remyelination of nerve cells in in vitro and in vivo models, such as cultures of neural progenitor and stem cells, cerebellar organotypic cultures, the zebrafish and the cuprizone-mediated demyelination mouse models.

RESULTS

In all, 13 compounds were identified and characterized, after a secondary screening, for inducing the differentiation of oligodendrocyte progenitor cells and for promoting myelination and remyelination in vitro and in vivo.

CONCLUSION

The 13 compounds, promoting the differentiation of oligodendrocyte progenitor cells and myelination of nerve cells, may be used for the treatment of multiple sclerosis (MS) and other myelin-related disorders. The application claims the use of the compounds to promote the differentiation of oligodendrocyte progenitor cells and endogenous remyelination for the treatment of demyelinating diseases alone or in combination with other agents and drugs, such as immunomodulatory, immunosuppressive, neuroprotective and neuroregenerative agents.

摘要

背景

该应用属于细胞治疗和神经修复领域。

目的

旨在鉴定和表征能促进少突胶质前体细胞分化和神经系统髓鞘再生的化合物和分子。

方法

在一系列专门设计和开发的实验中对化合物库和分子库进行筛选,以评估化合物和分子在体外和体内模型中对少突胶质前体细胞分化和神经细胞髓鞘再生的活性和效力,这些模型包括神经祖细胞和干细胞培养物、小脑器官型培养物、斑马鱼和杯状胶诱导的脱髓鞘小鼠模型。

结果

经过二次筛选,共鉴定和表征了 13 种化合物,它们能诱导少突胶质前体细胞分化,并促进体外和体内的髓鞘形成和髓鞘再生。

结论

这 13 种促进少突胶质前体细胞分化和神经细胞髓鞘形成的化合物,可用于治疗多发性硬化症(MS)和其他与髓鞘相关的疾病。该申请要求使用这些化合物来促进少突胶质前体细胞分化和内源性髓鞘再生,单独或与其他免疫调节、免疫抑制、神经保护和神经再生药物联合用于治疗脱髓鞘疾病。

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