Scientists Uncover Mechanism Behind Neuron Death in Multiple Sclerosis

Breakthrough discovery explains damage to brain's gray matter in MS patients

Apr. 7, 2026 at 6:46pm by Ben Kaplan

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A highly structured abstract painting in muted earth tones, featuring sweeping geometric arcs, concentric circles, and precise botanical spirals, visually representing the complex mechanisms of DNA damage and neuron death in multiple sclerosis.A conceptual illustration of the DNA damage and neuron death process uncovered in multiple sclerosis, providing new insights into the disease's impact on the brain's gray matter.San Francisco Today

A team of scientists from UC San Francisco, University of Cambridge, and Cedars-Sinai Medical Center has made a breakthrough discovery in understanding the mechanism behind neuron death in multiple sclerosis (MS). The researchers found that inflammation in the brain during MS leads to DNA damage in a specific subset of neurons, called CUX2 neurons, which are critical for higher cognitive function. This DNA damage overwhelms the neurons' natural repair systems, causing them to die off.

Why it matters

This discovery is significant because it helps explain why brain scans of people with MS reveal damage not only to the white matter (the brain's wiring), but also to the gray matter, which houses the neurons responsible for higher thinking and cognition. Previous MS research has primarily focused on the loss of myelin, the insulation around nerve fibers, but this new understanding of neuron death in the gray matter opens up a new front in the fight against the debilitating effects of MS.

The details

The researchers found that in mouse models of MS, inflammation triggers chemical reactions that damage the DNA in CUX2 neurons, a specific subset of neurons in the brain's gray matter. These neurons normally have robust DNA repair mechanisms to cope with the stresses of rapid growth and development early in life. However, the inflammation overwhelms these repair systems, leading to widespread DNA damage and neuron death. The team also found evidence of this same DNA damage process occurring in gray matter lesions from people with MS.

  • The findings were published on April 1, 2026 in the journal Nature.

The players

Steve Fancy

A professor in the UCSF Weill Institute for Neurosciences and the co-corresponding author of the two studies.

Stephen Hauser

The Robert A. Fishman Distinguished Professor in Neurology who directs the UCSF Weill Institute for Neurosciences.

David Rowitch

The deputy director for Research at Guerin Children's, professor of Paediatrics at the University of Cambridge, and co-corresponding author of the studies.

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What they’re saying

“It's become clear that in addition to promoting remyelination (rebuilding myelin) in progressive MS, it's essential to find ways to directly protect grey matter neurons themselves.”

— Steve Fancy, Professor, UCSF Weill Institute for Neurosciences

“We've had remarkable success developing therapies to slow the loss of myelin during MS, but grey matter lesions and the disability they cause have been harder to address.”

— Stephen Hauser, Robert A. Fishman Distinguished Professor in Neurology, UCSF

“The CUX2 neurons are like a 'canary in the coal mine' for the brain affected by MS. If we can protect these neurons, we might be able to contain the damage before the disease progresses.”

— David Rowitch, Deputy Director for Research, Guerin Children's; Professor of Paediatrics, University of Cambridge

What’s next

The researchers plan to further investigate ways to directly protect the vulnerable CUX2 neurons in the brain's gray matter, in addition to continuing efforts to promote remyelination of white matter. This new understanding of the mechanism behind neuron death could lead to the development of novel therapies to address the debilitating cognitive and functional impacts of multiple sclerosis.

The takeaway

This discovery represents a significant breakthrough in understanding the complex mechanisms underlying multiple sclerosis, particularly the damage to the brain's gray matter that contributes to cognitive and functional impairments. By identifying the vulnerable CUX2 neurons as a key target, researchers now have a new avenue to explore potential therapies that could help preserve critical brain functions in MS patients.