Study of mTOR Signaling Inhibitors as Potential Treatment for TSC
Abstract
The most significant finding during the research period (max 200 words) purpose, scope, major findings and be an up-to-date report of the progress in terms of results and significance. Subject terms are keywords that may have been previously assigned to the proposal abstract or are keywords that may be significant to the research. The goal of this project 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. The effect of the drugs on mTORC1 signaling, cell viability, serum-independent proliferation, p27 nuclear localization, cell motility, cell morphology, cell size, cell-cell contacts and focal adhesions were determined in TSC2+/+ and TSC2-/- mouse embryo fibroblasts. Two drugs, nitazoxanide and tizoxanide, did not significantly inhibit mTORC1 in these cells. Four additional drugs, perhexiline, amiodarone, dronedarone and niclosamide were able to reverse the abnormal epithelial-like morphology of TSC2-defective fibroblasts to a more normal fibroblastic morphology, which may indicate therapeutic potential.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2013
- Accession Number
- ADA601809
Entities
People
- Michel Roberge
Organizations
- University of British Columbia