In Sporadic ALS Model, Nervous System Support Cells Are Toxic to Motor Neurons

February 21, 2014

Scientists at Columbia University in New York have discovered new insights into the causes of motor neuron death in ALS. These findings are likely to lead to testing of new therapeutic strategies to slow the disease’s progression.

Past work has shown that an unknown toxic property of supporting cells known as astrocytes contributes to the death of motor neurons in ALS. Much of that work has been done in a disease model with artificially elevated levels of the ALS-causing protein, superoxide dismutase (SOD). To test whether a similar mechanism was at work without that protein elevation, the researchers at Columbia grew astrocytes from individuals with ALS who have the sporadic (non-familial) form of the disease and exposed them to human motor neurons from healthy embryonic stem cells. This is one of the first times that scientists have produced a “fully humanized” model of sporadic ALS that combines astrocytes and motor neurons.

The researchers discovered that motor neurons succumbed to the toxic effects of the astrocytes, through a specific process of cell death called necroptosis. Because this process is at least partially understood on the molecular level, it should be possible to design treatments to interrupt it, which may be therapeutic.

The research was performed by Diane Re, Ph.D., and Virginia Le Verche, Ph.D., under the leadership of Serge Przedborski, M.D., Ph.D., and was funded by The ALS Association, Greater New York Chapter. The study appears in the journal Neuron.

“These exciting results shed new light on the interaction between motor neurons and astrocytes,” said Lucie Bruijn, Ph.D., Chief Scientist for The Association. “The finding that astrocytes from sporadic ALS patients exert toxicity will strengthen the focus on understanding this interaction more closely and point out possible new targets for therapy.”

Read the press release.

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