Chemical Genetic Screens for TDP-43 Modifiers and ALS Drug Discovery
Abstract
Our objective was to screen libraries of several thousand clinically approved drugs for their ability to suppress the in vivo phenotypes observed in both worm and fish models upon expression of mutant TDP-43 related to ALS. Our hypothesis is that chemical modifiers of TDP-43 in vivo function will provide new therapeutic approaches to ALS. The screen set-up (Aim 1) began immediately for worms and fish during the first 6 months. This consisted of developing video microscopy screens for motility. The first chemical screen (3,500 FDA-approved compounds, Aim 2) began immediately afterwards in worms and was completed during the second half of the year. As hits were identified, the 20 active compounds were rescreened in worms and fish. Most of the active compounds were neuroleptics with the most potent (acting at <1 M) being pimozide. This work was done by PIs Drapeau, Kabashi and Parker.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2012
- Accession Number
- ADA579919
Entities
People
- Pierre Drapeau
Organizations
- Université de Montréal