Methods for drug discovery using stem cell-derived schwann cells

a technology of drug discovery, which is applied in the field of drug discovery using stem cell-derived schwann cells, can solve the problems of increased morbidity and mortality, no effective treatment of dpn, and reduced quality of li

Pending Publication Date: 2019-10-31
MEMORIAL SLOAN KETTERING CANCER CENT +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

It represents a major health problem causing reduced quality of life and increased morbidity and mortality (La Fontaine et al., 2014).
There are currently no effective treatments for DPN other than pursuing the primary goal of preventing further damage by carefully monitoring and adjusting glucose levels.
Dissecting cell type specific mechanisms is very challenging in current animal models of DPN given the complex contribution of non-cell autonomous factors including systemic vascular abnormalities to the disease phenotype.

Method used

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  • Methods for drug discovery using stem cell-derived schwann cells
  • Methods for drug discovery using stem cell-derived schwann cells
  • Methods for drug discovery using stem cell-derived schwann cells

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SUMMARY

[0214]Schwann cell precursors and Schwann Cells were derived from human stem cells (e.g., hPSC). The inventors established an hESC-based in vitro model of DPN that revealed the selective vulnerability of human SCs to hyperglycemia-induced cytotoxicity and activation of the polyol pathway. The inventors further used this model to perform high throughput drug screening and identified Bupropion as a compound for treatment of DPN. Bupropion can counteract the high-glucose induced cytotoxicity in SCs in vitro and rescues the neuropathy related histological and behavioral deficits in STZ-treated diabetic mice.

Methods and Materials

[0215]Culture of Undifferentiated Human Embryonic Stem Cells (hESCs)

[0216]hESC line H9 (WA-09) and derivatives (SOX10::GFP; SYN::ChR2-YFP; SYN::YFP;PHOX2B:GFP; EF1::RFP EDNRB− / −) as well as 2 independent hiPSC lines (healthy and Familial Dysautonomia, Sendai-based, OMSK (Cytotune)) were maintained on mouse embryonic fibroblasts (MEF, Global Stem, Rockville...

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Abstract

The presently disclosed subject matter relates to use of Schwann cell precursors and Schwann cells derived from stem cells (e.g., human stem cells) for drug discovery in regeneration of peripheral nervous system (PNS) and / or central nervous system (CNS), prevention and / or repair myelin damages, and / or prevention and / or treatment of Schwann cell-related disorder (e.g., peripheral neuropathy diabetic peripheral neuropathy).

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application is a Continuation of International Patent Application No. PCT / US17 / 61549 filed Nov. 14, 2017, which claims priority to U.S. Application No. 62 / 421,816 filed Nov. 14, 2016, and the contents of each of which are hereby incorporated by reference in their entireties herein, and to each of which priority is claimed.INTRODUCTION[0002]The presently disclosed subject matter relates to use of Schwann cell precursors and Schwann cells derived from stem cells (e.g., human stem cells) for drug discovery in regeneration of peripheral nervous system (PNS) and / or central nervous system (CNS), prevention and / or repair of myelin damages, and / or prevention and / or treatment of Schwann cell-related disorder (e.g., peripheral neuropathy diabetic peripheral neuropathy). It further provides for methods of treatment of Schwann cell related disorders using compounds identified by said drug discovery materials and methods.BACKGROUND[0003]Schwann c...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): G01N33/50C12N5/079
CPCC12N5/0622C12N2506/02G01N33/5038C12N2501/115G01N33/5058C12N2501/01A61K35/30A61P19/00A61K35/28C12N2501/15C12N2501/415G01N33/5073C12N5/0062C12N2501/113C12N2501/117C12N2501/119C12N2501/999C12N2513/00
Inventor STUDER, LORENZFATTAHI, FARANAKGHAZIZADEH, ZANIARCHEN, SHUIBING
Owner MEMORIAL SLOAN KETTERING CANCER CENT
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