Identification of Disease Mechanisms and Potential Therapeutic Targets for ALS and FTD Using Stem Cells

We have used patient-specific stem cell technology to uncover a surprising interplay between gain- and loss-of-function disease mechanisms in the most common form of ALS and FTD, caused by a repeat expansion mutation in C9ORF72. In addition, we have used high-throughput chemical screens on patient-derived neurons to identify novel therapeutic targets for C9ORF72 and sporadic ALS. Recently, we have developed a systematic approach for the identification of gene variants that cause sporadic ALS and are using it to investigate potential new ALS genes with key roles in proteostasis.