Study of mTOR Signaling Inhibitors as Potential Treatment for TSC
Revised annual rept. 1 Jul 2011-30 Jun 2012
BRITISH COLUMBIA UNIV VANCOUVER
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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.
- Medicine and Medical Research