Developing ER Stress Inhibitors for Treating ALS

Abstract

We have developed ASK1 inhibitors for the reduction of ER stress and the treatment of ALS. These compounds were screened in cellular models ALS and lead compounds were assessed in zebrafish models of ER stress. Two lead compounds were identified that are protective against ER stress-induced neuronal death. ALS mouse models were treated with compounds that modulate neuronal signaling and demonstrate favorable pharmacokinetics, however; no significant differences in age of symptom onset or survival were observed. Testing and development of these compounds is ongoing.

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Document Details

Document Type
Technical Report
Publication Date
Nov 01, 2015
Accession Number
AD1002708

Entities

People

  • Nicholas Cosford

Organizations

  • Sanford Burnham Prebys Medical Discovery Institute

Tags

DTIC Thesaurus Topics

  • Biological Sciences
  • Biomedical Research
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Chemical Synthesis
  • Chemistry
  • Diseases And Disorders
  • Endoplasmic Reticulum
  • Genetically Modified Organisms
  • Lead Compounds
  • Motor Neurons
  • Neurodegeneration
  • Neurodegenerative Diseases
  • Neurosciences
  • Organic Chemistry
  • Small Molecules

Fields of Study

  • Chemistry

Readers

  • Cellular and Molecular Pathways of Apoptosis.
  • Immunology and Pathology
  • Toxicology/Environmental Toxicology