The brain damage starts long before the tremors, the vision problems, or the fatigue that sends people to the neurologist. Scientists at UC San Francisco have traced the biological roots of multiple sclerosis back seven years before diagnosis, a discovery that reveals the disease’s stealthy assault on the nervous system during a period when patients feel completely healthy.
By analyzing more than 5,000 proteins in blood samples from 134 people who would eventually develop MS, researchers found that the immune system begins shredding the protective myelin coating around nerve fibers years before any symptoms appear. The myelin damage shows up first, followed about a year later by injury to the nerve fibers themselves. It is a sequence that suggests a cascade: first the insulation fails, then the wires start to fray.
The study, published in Nature Medicine, relied on an unusual resource: blood samples collected from military service members when they joined the armed forces, then stored by the Department of Defense for decades. Some of those healthy young recruits would later develop MS, giving scientists a chance to rewind the clock and watch the disease emerge in slow motion.
A Protein Called MOG Appears First
Seven years before diagnosis, the researchers spotted a spike in MOG, short for myelin oligodendrocyte glycoprotein. The name is technical, but the meaning is clear: myelin is breaking down. A year after that initial spike, another protein called neurofilament light chain began rising in the blood, signaling that the nerve fibers themselves were now under attack.
During this presymptomatic window, the blood also showed elevated levels of immune signaling proteins, particularly one called IL-3. This protein is known for recruiting immune cells to the brain and spinal cord, where they mistakenly attack the body’s own nerve tissue. Ahmed Abdelhak, an assistant professor of neurology at UCSF and first author of the study, noted the implications for early intervention:
“We think our work opens numerous opportunities for diagnosing, monitoring, and possibility treating MS. It could be a gamechanger for how we understand and manage this disease.”
The researchers identified about 50 proteins that appear to herald future disease. They have filed a patent application for a diagnostic blood test using the top 21 of them. Whether such a test would be practical or cost-effective remains to be seen, but the science suggests it is at least theoretically possible to catch MS before it announces itself with clinical symptoms.
Implications for Prevention
The findings raise an obvious question: if the disease can be detected years before symptoms appear, could it also be stopped? Ari Green, chief of the Division of Neuroimmunology and Glial Biology at UCSF and senior author of the paper, framed the discovery in cautiously optimistic terms:
“We now know that MS starts way earlier than the clinical onset, creating the real possibility that we could someday prevent MS, or at least use our understanding to protect people from further injury.”
MS affects roughly one million people in the United States, most of them diagnosed in their twenties or thirties. The disease is unpredictable: some patients experience mild symptoms for decades, while others progress rapidly to severe disability. Current treatments can slow the disease but not reverse the damage already done. The earlier a patient starts treatment, the better the outcome tends to be.
The new research suggests that by the time a patient walks into a clinic with their first neurological complaint, the immune system has already been attacking their brain for years. That silent period, when myelin is being destroyed but nerve function remains mostly intact, could be the ideal window for intervention. Whether doctors will one day screen high-risk populations for presymptomatic MS, much as they now screen for high cholesterol or prediabetes, is a question for future research.
For now, the study offers a clearer picture of what MS looks like in its earliest stages. The disease does not arrive suddenly. It builds slowly, protein by protein, year by year, until the damage crosses some threshold and symptoms finally break through.
Nature Medicine: 10.1038/s41591-025-03436-z
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