Who would have guessed that pouring ice water on one’s head would lead to $94.3 million in donations (and counting) to fund Amyotrophic lateral sclerosis (ALS) research? Well it did. And it’s a great thing – ALS is a devastating neurodegenerative disease in which progressive death of motor neurons causes debilitating and eventually fatal paralysis. There are no cures and very few therapies available. However, an exciting recent report from researchers at the Harvard Stem Cell Institute proposes a new potential target for ALS therapy. Perhaps even more exciting is the particular progression of the experiments: using mice, this research validates a potential therapeutic target of ALS originally discovered in human stem cells. These results demonstrate that discoveries made using stem cells in a dish can provide valuable insight into how a disease works in live animals! The next tricky step, however, is figuring out whether this enticing new target for ALS therapy will prove successful in human patients.

Most cases of ALS spontaneously develop with no known cause, however a small subset (~2%) are caused by an inherited genetic mutation in a protein called superoxide dismutase. The vast majority of ALS research is done by studying mice genetically manipulated to carry the same mutation, causing them to have this specific form of familial ALS. However it’s still not clear how this mutation results in motor neuron death.

In a previous study, the same researchers found that it may not entirely be the motor neurons’ fault. Using stem cells in a dish, they showed that glia (non-neuronal brain cells) became toxic to healthy motor neurons when superoxide dismutase was mutated. In this current study, they went on to identify the specific protein in glia that renders them toxic to motor neurons. Using this finding, they hypothesized that reducing this protein in the mouse model for ALS might be beneficial. They were right! Genetically deleting the glial protein actually increased the lifespan of the mice by ~10%.

So what’s next? Unfortunately, therapeutic targets identified in mice are not always efficacious in humans. This has been especially true in ALS research, where the mouse model of ALS mimics only a small fraction of human cases. While this research represents an incredibly important first step, there are many other factors to be considered and investigated in order to find and implement a safe and successful therapy.

More generally, however, this research represents an exciting proof of principle that discoveries made in stem cells can be used to valuably guide research in animal models of disease and, hopefully, in furthering our understanding of human disease.

Edited by SITN Waves editor Shay Neufeld. Special thanks to Sophie de Boer, neuroscientist at Harvard Stem Cell Institute and the first author on the study, for her helpful correspondence . 

Kevin Eggan, whose lab conducted the study, challenged the President of Harvard, Drew Faust, to the ice bucket challenge. Watch it here.