Researchers Uncover Key Mechanism Behind MS Neuron Destruction

New findings point to DNA damage as a driver of neuron loss in the brain's gray matter during multiple sclerosis.

Apr. 2, 2026 at 2:02am by Ben Kaplan

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A team of researchers from UC San Francisco, University of Cambridge, and Cedars-Sinai Medical Center has uncovered a key mechanism behind the destruction of neurons in the brain's gray matter during multiple sclerosis (MS). The scientists found that inflammation in MS triggers chemical reactions that damage the DNA of specific neurons, leading to their death. This helps explain why brain scans of people with MS show damage not only to the white matter, but also to the gray matter, which houses the brain's nerve cell bodies.

Why it matters

This discovery represents an important shift in MS research, which has traditionally focused on the loss of myelin, the insulation around the brain's wiring. The new findings indicate that directly protecting the vulnerable neurons in the brain's gray matter is essential for fighting the progression of MS, in addition to promoting remyelination. Understanding the underlying mechanism of neuron destruction opens up new avenues for developing therapies to preserve brain function in people with MS.

The details

The researchers focused on a specific type of neuron in the brain's outer layer, or cortex, that expresses a gene called CUX2. They found that in mouse models of MS, inflammation triggers chemical reactions that damage the DNA of these CUX2 neurons. The neurons' natural DNA repair mechanisms, which are critical for their survival during brain development, can no longer keep up with the onslaught of damage, leading to neuron death.

  • The two studies were published on April 1, 2026 in the journal Nature.
  • The research team has been studying the role of gray matter neuron loss in MS for several years.

The players

Steve Fancy

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

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 in progressive MS, it's essential to find ways to directly protect grey matter neurons themselves.”

— Steve Fancy, Professor, UCSF Weill Institute for Neurosciences

“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 continue investigating ways to directly protect the vulnerable neurons in the brain's gray matter as a new approach to treating MS and preventing further cognitive decline.

The takeaway

This breakthrough in understanding the mechanism behind neuron destruction in the gray matter of the MS-affected brain represents a significant shift in the field, moving beyond the traditional focus on white matter damage. Developing therapies to preserve these critical neurons could be key to containing the progression of MS and preserving brain function.