First human cell model for Huntington’s shows value of consortium science

Image of striatal neuron (yellow) which is damaged in
Huntington's disease (credit: Dr. Steven Finkbeiner)

We have written often, most recently last week, about the power of using stem cells reprogrammed from a patient’s skin to recreate the patient’s disease in a dish. You simply take a skin sample, or other tissue sample, and use one of many proven techniques to trick that adult tissue into thinking it is like embryonic stem cells. After that you use various chemicals and other tools to tell those stem cells to mature into the tissue impacted by the disease.

But the real trick is verifying that those nerve cells, or what ever you have in the dish, really are behaving like those same cells in the patient.

Now, a ten-institution international consortium says they have verified the validity of model cell lines made from several Huntington’s disease patients. A team led by Clive Svendsen at Cedars-Sinai, with the help of a CIRM-funded post doctoral fellow, made the cell lines. They then shared those cells with all the consortium members. They were able to mature them into the types of nerve cells that control movement and cognition—the ones impacted by Huntington’s. More important, they consistently found the same difference in those cells compared to normal nerve cells. In particular, the model cells were much more susceptible to the researchers creating “stressful” condition in the petri dish. The model cells were much more likely to die, as happens in the disease.

A press release from Cedars-Sinai quotes Svendsen, who is director of their Regenerative Medicine Institute.

This Huntington’s ‘disease in a dish’ will enable us for the first time to test therapies on human Huntington’s disease neurons. In addition to increasing our understanding of this disorder and offering a new pathway to identifying treatments, this study is remarkable because of the extensive interactions between a large group of scientists focused on developing this model. It’s a new way of doing trailblazing science.

The cell lines have been made available via a National Institutes of Health-funded repository at Coriell Institue in New Jersey.

CIRM funds $9.7 million in grants for projects in California trying to solve the Huntington’s dilemma, including one to Leslie Thompson at UC Irvine to participate in this consortium. The full list is here.

D.G.