Case Western Reserve University

Paul J Tesar

Fadi J Najm

Robert H Miller

Drew Adams

Steven B Landau

Zita Hubler

Dharmaraja Allimuthu

Matthew Elitt

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 an agent that enhances and/or induces accumulation of Δ8,9-unsaturated sterol intermediates of the cholesterol biosynthesis pathway in the oligodendrocyte precursor cells.

Compounds and methods of promoting myelination

Disclosed is a pharmaceutical composition comprising a compound represented by Structural Formula (I): or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent. Also disclosed is a method of treating a myelin related disorder in a subject, the method comprising administering to the subject an effective amount of a compound of Structural Formula (I) or a pharmaceutical composition comprising the compound of Structural Formula (I). The variables of Structural Formula (I) are described herein.

Compounds for treating myelin related disorders

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 an agent that enhances and/or induces accumulation of &#x394;8,9-unsaturated sterol intermediates of the cholesterol biosynthesis pathway in the oligodendrocyte precursor cells.

A method of generating a cell that enhances functional myelin production is provided, the method including genetically modifying the cell such that: (i) an endogenous PLP1 gene is modified to decrease its ability to inhibit myelin production; (ii) an endogenous PLP1 genetic regulatory element is modified to decrease its ability to promote PLP1 expression; (iii) an endogenous PLP1 genetic regulatory element is modified to increase its ability to inhibit PLP1 expression; or (iv) an endogenous PLP1 gene product or a PLP1 regulatory element gene product that promotes PLP1 expression is modified to decrease the PLP1 expression level, wherein the cell produces functional myelin.

Methods and compositions for enhancing functional myelin production

The invention is a method of treating a subject with primary progressive or secondary progressive multiple sclerosis. The method comprises administering an effect amount of Cis-N-cyclohexyl-N-ethyl-3-(3-chloro-4-cyclohexylphenyl)prop-2-enylamine or a pharmaceutically acceptable salt thereof to the subject.

A method of promoting remyelination in a subject in need thereof includes administering to the subject a therapeutically effective amount of at least one (1,3) Diazole compound, wherein the therapeutically effective amount is the amount effective to induce endogenous oligodendrocyte precursor cell (OPC) differentiation in the subject's central nervous system.

Method of promoting remyelination

The present invention relates to the reprogramming of differentiated somatic cells, such as those differentiated cells that arise from embryonic mesoderm, into glial cells. Glial cells produced from this reprogramming are functionally equivalent to glial cells that arise from ectodermal origins.

Cell fate conversion of differentiated somatic cells into glial cells

The present invention provides methods for generating oligodendrocyte progenitor cells from pluripotent cells, as well as methods for sustaining these oligodendrocyte progenitor cells in relatively pure cultures for long periods of time. The present invention also provides methods for further differentiating these oligodendrocyte progenitor cells into various glial cells.

Growing community of inventors

Cleveland, OH, United States of America

Paul J Tesar