Study of mTOR Signaling Inhibitors as Potential Treatment for TSC

Abstract

The goal in year 1 of this award was to determine the extent to which six drugs reduce or normalize the pathologically high mTORC1 activity seen in TSC-defective cells, to determine whether they can improve other abnormal phenotypes described for TSC-defective cells, and to select a candidate for proof of concept in animal studies in year 2. The effect of drugs on mTORC1 signaling, cell viability, serum-independent proliferation, p27 nuclear localization and cell motility were determined in TSC2+/+ and TSC2-/- cells. Two drugs, nitazoxanide and tizoxanide, did not significantly inhibit mTORC1 in these cells. Three additional drugs, perhexiline, amiodarone and niclosamide appear too toxic to be viable drugs for treatment of tuberous sclerosis. Dronedarone is the only drug with potential for in vivo testing.

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2012
Accession Number
ADA581647

Entities

People

  • Betty Diamond
  • Michel Roberge

Organizations

  • University of British Columbia

Tags

DTIC Thesaurus Topics

  • Biomedical Research
  • British Columbia
  • Cell Line
  • Cell Movement
  • Cells
  • Culture Techniques
  • Fluorescence
  • Fluorescent Dyes
  • Inhibition
  • Inhibitors
  • Membranes
  • Microscopy
  • Phenotypes
  • Sclerosis
  • Viability
  • Wound Healing

Fields of Study

  • Medicine

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