More than a million Americans live with multiple sclerosis, yet the disease remains stubbornly unpredictable—symptoms can flare up and fade over days, months, or even years, leaving patients grappling with crushing fatigue, muscle spasms, and vision loss. Understanding what happens inside the nervous system during an MS attack is the key to developing new treatments, and neurobiologist Katrina Adams at the University of Notre Dame has just delivered a crucial piece of that puzzle.
MS damages myelin, the fatty protective coating that insulates nerve fibers like plastic around electrical wires. When myelin breaks down, it creates lesions—damaged patches that vary wildly in size and location throughout the brain, optic nerves, and spine. Scientists have relied on two main laboratory models to study this damage: cuprizone (CPZ) and lysophosphatidylcholine (LPC). For years, researchers have used these models almost interchangeably, assuming they were largely equivalent. A new study published in Nature Communications by Adams' research group reveals that assumption was wrong—and the differences matter enormously.
The research, conducted in the Galvin Life Science Center, shows that while both models degrade myelin, they do so on completely different timelines and in different patterns. CPZ causes widespread myelin loss across the nervous system over several weeks, creating a slow, gradual deterioration. LPC, by contrast, triggers a concentrated lesion in a single location within just days, with a much sharper, more aggressive response. "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," Adams said.
These differences have profound implications for which model researchers should use depending on their specific question. If scientists want to understand what happens to myelin-producing cells—whether they're stressed, dying, or attempting to repair themselves—CPZ is the better choice because the gradual damage mirrors real MS progression more closely. But if researchers are investigating how immune cells respond to myelin loss, LPC is superior, since its aggressive immune activation more accurately reflects what happens in human patients.
Adams' team went further, comparing genetic maps created from both models against tissue samples from actual MS patients using single-cell RNA sequencing. This crucial step—matching laboratory models to real human disease—ensures that treatments developed in the lab will actually target what's happening in patients. "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 explained. The genetic analysis revealed surprising variations between the two models that the team doesn't yet fully understand—variations that may hold clues to whether cells can regenerate lost myelin.
This matters because today's MS treatments focus almost entirely on suppressing the immune system's destructive attack on nerve tissue. Myelin regeneration, by contrast, remains an untapped drug target with enormous potential. The strategic use of these two distinct preclinical models provides the roadmap researchers need to finally translate laboratory insights into therapies that could restore what MS has stolen—the protective coating that lets our nervous systems do their job.