Editorial on the original article entitled "Genetic validation of a therapeutic target in a mouse model of ALS" published in the Science Translational Medicine on August 6, 2014.

Amyotrophic lateral sclerosis (ALS) still remains a deadly neurodegenerative disease, mainly characterized by the combined degeneration of both upper and lower motor neurons (MNs). The pathology perspective is changed after 2006 due to the demonstration of common inclusions in ALS and Frontotemporal Dementia (non-tauFTD). Genetics largely contributed to further define the common mechanisms of both diseases but the large numbers of sporadic cases still remain unsolved. Transgenic mice models demonstrated the non-cell autonomous nature of ALS, being surrounding cells as astrocytes, microglial cells, and olygodendrocytes crucial in determining MN degeneration. More recently, the use of embryonic stem cells (ESCs) and/or IPSCs contributed to provide in vitro models for the ALS pathology and biological assay of clinical relevance. The combined use of ESC and SOD1 transgenic model of ALS has been pioneering used. The prostanoid receptor DP1 has been elegantly demonstrated to mediate the glial toxicity to stem-cell derived MNs in vitro. This evidence has been translated in vivo: the genetic ablation of DP1 in the SOD1G93A mice extended life span, decreasing microglial activation and MN loss. This paper is quite compelling, at the cutting edge of the stem cell-transgenic translation, demonstrating that discoveries derived from stem cells can be corroborated in vivo and possibly translated to humans.