This abstract was selected by our Scientific Committee to pitch on the programme in the R2B session (PM).
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that progressively and irreversibly affects motor movement due to the death of motor neurons in the brain and spinal cord. Mutations in over 20 genes have been associated with familial ALS with mutations in 4 genes accounting for the majority of familial cases - SOD1, FUS, TDP-43 and C9orf72.
Charles River has established cultures of human induced pluripotent stem cells (hiPSCs) from two control and four ALS patients, with each patient cell line harboring a mutation in one of the 4 genes which account for the majority of familial ALS. We have optimized a robust motor neuron differentiation protocol that is amenable to high throughput screening. Using this protocol, approximately 80-85% of the differentiated neurons express mature motor neuron markers, such as ISLET-1 and MNX1.
This physiologically relevant cell system combined with a scalable differentiation protocol, allows for high throughput screening of small molecule libraries or functional genomics-type approaches (RNAi/ CRISPR-Cas9), using high content imaging or biomarker readouts. Some of the disease relevant readouts that have been developed for screening are described below.