Researchers Compare MS Models to Human Tissue in Search for Better Therapies

Researchers identified key differences between two widely used multiple sclerosis models, showing how each can better study myelin damage, immune responses, and repair. The findings may improve efforts to develop treatments that restore lost myelin.

More than 1 million people in the United States are living with multiple sclerosis (MS), a disease that damages the brain, spinal cord, and optic nerves. Symptoms can appear suddenly and disappear just as unpredictably, sometimes lasting days, months, or even years. Common symptoms include severe fatigue, muscle spasms, and vision problems. Researchers say understanding how MS damages the nervous system is essential for developing better treatments.

Katrina Adams, a neurobiologist at the University of Notre Dame, studies how the loss and repair of myelin contribute to MS progression. Myelin is a fatty protective layer that surrounds nerve fibers and helps electrical signals travel efficiently through the nervous system, much like insulation around electrical wires. In MS, damage to myelin leads to inflammation and the formation of lesions that can differ in size, number, and location.

Since obtaining usable tissue samples from patients with progressive MS is difficult, scientists often depend on preclinical models to study the disease. In a new study published in Nature Communications, Adams and her team directly compared two widely used models for studying myelin damage and repair: cuprizone (CPZ) and lysophosphatidylcholine (LPC).

“Our analysis of these two models of myelin loss and regeneration provides a road map based on robust scientific evidence that we hope will advance the study of MS and related diseases,” said Adams, who is the Gallagher Assistant Professor in the Department of Biological Sciences.

Comparing CPZ and LPC Models for MS Research

Although CPZ and LPC are often used for similar purposes, they produce different patterns of myelin damage. CPZ triggers widespread myelin loss over several weeks, while LPC creates a localized lesion within days. The study, funded by the National Multiple Sclerosis Society, identified situations where one model may be more useful than the other depending on the aspect of MS being studied.

“If you’re studying the myelin-producing cells and what’s happening to them in MS — are they stressed, dying or trying to repair? — CPZ is better, since the loss of myelin is more gradual,” Adams said. “For studying the immune cells that respond to the myelin loss, LPC may be better, since the immune response is more aggressive than in CPZ.”

The researchers also compared lesions from both preclinical models with tissue samples from people with MS. Using single-cell RNA sequencing, the team created genetic maps that revealed how cells changed in response to demyelination.

“By matching each model to features seen in diseased tissue from real patients, we can be sure that we’re targeting things that are actually causing disease in human patients,” Adams said. “There are so many potential paths to follow, so we want to make sure that the path chosen has direct relevance to MS patients.”

Genetic Insights Into Myelin Regeneration

The study also uncovered important genetic differences between the two models, which Adams’ group plans to investigate further.

“We were surprised to see several interesting genetic variations in some cell types, but we don’t yet know if these changes encourage or discourage myelin regeneration,” Adams said. “Learning more about these shifts in gene expression may reveal how MS affects the nervous system and how the body responds to it, which is essential groundwork for developing new therapies.”

Current MS treatments mainly focus on suppressing the immune system’s attack on lesions and nearby healthy tissue. However, restoring damaged myelin remains a major goal that researchers have not yet achieved.

“The strategic use of these two preclinical models is essential for translating insights into therapies that might restore lost myelin,” Adams said. “We need to better understand the very process of demyelination in order to treat one of the root causes of this debilitating disorder.”

Reference: “A comparative transcriptomic analysis of mouse demyelination models and multiple sclerosis lesions” by Erin L. Aboelnour, Veronica R. Vanoverbeke, Elizabeth A. Maupin, Madelyn M. Hatfield and Katrina L. Adams, 18 May 2026, Nature Communications.
DOI: 10.1038/s41467-026-72383-y

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