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Compounds and methods of promoting myelination

A compound, unsaturated technology, applied in the direction of medical preparations containing active ingredients, drug combinations, pharmaceutical formulations, etc.

Inactive Publication Date: 2019-05-21
CASE WESTERN RESERVE UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Less explored, however, is the hypothesis of enhanced myelination and / or remyelination by endogenous oligodendrocyte precursors or transplanted cells

Method used

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  • Compounds and methods of promoting myelination
  • Compounds and methods of promoting myelination
  • Compounds and methods of promoting myelination

Examples

Experimental program
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Embodiment Construction

[0288] In this example, we show that remyelination is mediated by oligodendrocyte progenitor cells (OPCs), an abundant stem cell population in the CNS and a major source of new myelinating oligodendrocytes. Loss of myelin-producing oligodendrocytes in the central nervous system (CNS) underlies many neurological disorders, including multiple sclerosis and a variety of genetic disorders. Using a high-throughput chemical screening approach, we have identified small molecules that promote myelination and functionally enhance remyelination in vivo by stimulating oligodendrocyte formation from OPCs. Here we demonstrate that a broad range of these myelin-promoting molecules act not through their canonical targets, but through direct inhibition of CYP51, sterol 14-reductase and EBP (a narrow range of enzymes in the cholesterol biosynthetic pathway). We found that chemical or genetic inhibition of these enzymes resulted in the accumulation of Δ8,9-unsaturated sterol intermediates, whic...

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Abstract

A method of promoting the generation of oligodendrocytes from oligodendrocyte precursor cells by enhancing their survival and / or maturation includes administering to the cell an effective amount of anagent that enhances and / or induces accumulation of delta8,9-unsaturated sterol intermediates of the cholesterol biosynthesis pathway in the oligodendrocyte precursor cells.

Description

[0001] related application [0002] This application claims priority to U.S. Provisional Application Nos. 62 / 367,416, filed July 27, 2016, and 62 / 452,204, filed January 30, 2017, the subject matter of which is incorporated herein by reference in its entirety. [0003] Government funding [0004] This invention was made with government support under Grant No. R01NS095280 awarded by the National Institutes of Health. The US Government has certain rights in this invention. Background technique [0005] Multiple sclerosis (MS) is a complex neurological disease characterized by the degeneration of central nervous system (CNS) myelin sheath. Composed mainly of lipids (70% lipid, 30% protein), this insulating substance protects the axon and enables skip conduction, which accelerates the axonal electrical impulse. Demyelination of axons in chronic MS can lead to axonal degeneration and neuronal cell death, but more specifically, MS destroys oligodendrocytes, the highly specializ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/4196A61K31/4178
CPCA61K31/7088A61P25/00A61P25/14A61P25/28A61P25/16A61P25/18A61K31/4196A61K31/138A61K31/4174A61K31/4535A61K31/4545A61K31/496A61K31/5375A61K31/198A61K38/16A61K38/215A61K31/137A61K45/06A61K39/3955A61K31/136A61K31/7105C12N9/50C12N15/1137
Inventor P.特萨D.亚当斯Z.胡布勒M.埃利特D.阿利穆图
Owner CASE WESTERN RESERVE UNIV
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