Year 3 FINAL

In the current study, we evaluated 10 FDA-approved drugs in neurons derived from ALS patient induced pluripotent stem cells using our robotic microscopy platform. Our goal was to find drugs that improve the survival of patient-derived neurons and ultimately to repurpose these drugs for ALS. We had previously found that some these drugs, through unknown mechanisms, have the capacity to jump-start the cell’s protein clearance mechanism called “autophagy”, and because of this, they could potentially help increase the survival of patient neurons. Of the 10 drugs we tested, we confirmed our previously published report of one drug that showed activity in neurons derived from an ALS patient with a rare genetic form of ALS involving the gene TDP43. We evaluated this drug in mice to see whether they have the capacity to enhance autophagy in the brain and spinal cord in a living animal. However, we did not find sufficient activity in the mouse model with this drug.