Therapeutic Targeting of Disrupted Nucleocytoplasmic Transport in C9orf72-ALS Motor Neurons

Abstract

Our proposed therapeutic development strategy is to carry out a screening campaign in order to identify small molecules that restore nucleocytoplasmic transport in C9ORF72 related amyotrophic lateral sclerosis. We developed a cell-based screening assay using nucleocytoplasmic transport biosensor. The sub-cellular localization of the biosensor can be assessed using high content imaging. In the second year of funding we began screening all compound libraries but encountered problems that substantially slowed our progress. We successfully overcame these problems and have now completed the primary screen of all libraries. However, due to the issues with quality control, we fell behind schedule and requested a no cost extension to allow us more time to complete the final validation experiments. The extension was approved and we finished the project by validating hits in U-2OS cells and iPSC neurons.

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Document Details

Document Type
Technical Report
Publication Date
Aug 01, 2020
Accession Number
AD1110710

Entities

People

  • Zane Zeier

Organizations

  • University of Miami

Tags

DTIC Thesaurus Topics

  • Acquisition
  • Biomedical Research
  • Biosensors
  • Cells
  • Disease Attributes
  • Diseases And Disorders
  • Gene Expression
  • Intellectual Property
  • Medical Personnel
  • Motor Neurons
  • Neurodegenerative Diseases
  • Quality Control
  • Small Molecules
  • Students
  • Therapy
  • Toxicity
  • Universities

Fields of Study

  • Biology

Readers

  • Medical Imaging.
  • Molecular Genetics
  • Systems Analysis and Design

Technology Areas

  • Biotechnology