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Screening platform to identify therapeutic drugs or agents for treatment of alzheimer's disease

A technology for therapeutic agents and substances, which is applied in the field of screening platforms for identifying therapeutic drugs or reagents for the treatment of Alzheimer's disease, and can solve problems such as unclear CD33 activity

Inactive Publication Date: 2020-05-15
THE GENERAL HOSPITAL CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

How these drugs interact and modulate the activity of CD33 is unknown

Method used

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  • Screening platform to identify therapeutic drugs or agents for treatment of alzheimer's disease
  • Screening platform to identify therapeutic drugs or agents for treatment of alzheimer's disease
  • Screening platform to identify therapeutic drugs or agents for treatment of alzheimer's disease

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Embodiment

[0118] overview

[0119] As indicated, compounds were selected and tested in microglia and 3D AD cell culture models at a range of concentrations and over time periods ranging from hours to days. Culture models were chosen to elucidate the different stages and biological aspects of Alzheimer's disease. Using a commercially available assay that measures LDH release (CytoTox-ONE TM , Promega) assay media to assess compound toxicity. Toxic concentrations were excluded from further testing. For microglial cultures, Aβ42 and Aβ40 uptake assays were performed for 2 to 24 hours after 3 hours of compound pretreatment. Alternatively, LPS-activation assays were performed for 3 hours after 3 hours of compound pretreatment. The reduction of toxic cytokines released in the culture medium was monitored.

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Abstract

Disclosed are methods and compositions for screening candidate substances for the prevention or treatment of neurodegenerative disorders such as Alzheimer's disease. The disclosure also relates to identifying the mechanisms of action for known or suspected Alzheimer's disease drugs and generally to compositions and methods for modulating the function of cells expressing CD33.

Description

[0001] related application [0002] This application claims the benefit of U.S. Provisional Application No. 62 / 530,125, filed July 8, 2017, and U.S. Provisional Application No. 62 / 535,589, filed July 21, 2017, under 35 U.S.C. § 119(e), which The content of each is incorporated herein by reference in its entirety. technical field [0003] The present disclosure generally relates to methods and compositions for screening candidate substances for the prevention or treatment of neurodegenerative disorders. The present disclosure also generally relates to compositions and methods for modulating the function of CD33-expressing cells. Background technique [0004] Neurodegenerative disease is a serious, pervasive and growing global problem. These include Alzheimer's disease (AD), cognitive impairment, Parkinson's disease, dementia, schizophrenia, amyotrophic lateral sclerosis (ALS), Huntington's disease or multiple sclerosis. Especially in the elderly, neurodegenerative diseases...

Claims

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Application Information

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IPC IPC(8): A61K31/381A61K31/397C07K14/47C07K16/28
CPCA61K31/381A61K31/397C07K14/47C07K16/28G01N33/5058A61P25/28G01N2333/70596G01N2500/04G01N2333/4709G01N2333/775C12N5/0619C12N2503/02C12N2513/00C12N2510/00A61P25/16G01N2333/52A61K38/00C07K16/2803G01N2400/50
Inventor 鲁道夫·E·坦济路易莎·昆蒂金斗渊
Owner THE GENERAL HOSPITAL CORP