Research ArticleAmyotrophic Lateral Sclerosis

Genetic validation of a therapeutic target in a mouse model of ALS

Science Translational Medicine  06 Aug 2014:
Vol. 6, Issue 248, pp. 248ra104
DOI: 10.1126/scitranslmed.3009351

You are currently viewing the abstract.

View Full Text
As a service to the community, AAAS/Science has made this article free with registration.


Neurons produced from stem cells have emerged as a tool to identify new therapeutic targets for neurological diseases such as amyotrophic lateral sclerosis (ALS). However, it remains unclear to what extent these new mechanistic insights will translate to animal models, an important step in the validation of new targets. Previously, we found that glia from mice carrying the SOD1G93A mutation, a model of ALS, were toxic to stem cell–derived human motor neurons. We use pharmacological and genetic approaches to demonstrate that the prostanoid receptor DP1 mediates this glial toxicity. Furthermore, we validate the importance of this mechanism for neural degeneration in vivo. Genetic ablation of DP1 in SOD1G93A mice extended life span, decreased microglial activation, and reduced motor neuron loss. Our findings suggest that blocking DP1 may be a therapeutic strategy in ALS and demonstrate that discoveries from stem cell models of disease can be corroborated in vivo.

View Full Text