Cells from people with amyotrophic lateral sclerosis (ALS) reveal how a mutation kills neurons, but also show how to reverse its effects.

In both ALS and frontotemporal dementia, the most common genetic abnormality is a repeated six-nucleotide motif in the gene C9ORF72. A team led by Rita Sattler and Jeffrey Rothstein, both at Johns Hopkins University in Baltimore, Maryland, took skin cells from people with ALS who carry this mutation, then turned them into induced pluripotent stem cells and directed these cells to become neurons. By studying the neurons, the team found that the mutation causes RNA transcripts to clump together with RNA-binding proteins, which alters gene expression and eventually causes cell death. Strings of 'antisense' nucleotides that bind to the mutation on C9ORF72 RNA template molecules reversed these effects.

The findings suggest that defective RNA processing contributes to both diseases, the authors say.

Neuron 80, 415–428 (2013)