Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two devastating neurodegenerative diseases which have overlap in pathological features and the genetic basis. We recently discovered that treating mouse neurons Analysis of neurons isolated from mice which carry a genetic alteration associated with human ALS/FTD, revealed a variety of defects including a change in the shape of the neurons and an increased sensitivity to a stress-inducing factor. We recently discovered that treating the neurons with a new drug, rescued these defects. Here, we propose to explore whether this drug might support survival and function of neurons in the context of ALS in the context of human neuronal models. For this, we will produce neurons in the laboratory using pluripotent cells generated from skin samples from ALS patients and then test the effect of the compounds on neuronal survival. We will also use the pluripotent patient-derived cells to make cerebral organoids, which are small three dimensional tissues that mimic brain tissue and thus is thought to be a better model to study disease processes and the potential efficacy of drugs. Results from our work will provide preclinical evidence for the effectiveness of this drug and if promising, will prompt further studies with the goal of translating our findings into the clinic. Since this drug is already being used for cancer patients, if successful, our work have the potential to rapidly and significantly improve and prolong the quality of life for ALS/FTD patients.
