Scientists have discovered hidden brain damage years before MS symptoms appear
By the time most people start seeking help for multiple sclerosis (MS), the disease has been quietly affecting the brain for years. Until recently, scientists weren’t sure which cells were affected first or when the damage actually started.
Track early attacks of the disease
Researchers at the University of California, San Francisco have now provided the most detailed timeline yet by analyzing thousands of proteins circulating in the blood. Their findings show that the immune system begins attacking the brain’s protective myelin sheath – the fatty covering that insulates nerve fibers – much earlier than scientists previously thought.
The team measured parts of myelin and other molecules left behind by immune attacks, along with chemical signals that drive the immune system’s response. This work has allowed them to identify, for the first time, the chain of biological events that ultimately lead to the onset of MS.
This discovery opens the door to early diagnosis and, in the future, may make prevention possible.
Early warning signs of the body
Research has shown that MS first targets the myelin sheath. After about a year, evidence of damage to the underlying nerve fibers begins to appear.
Among the immune-related proteins that rose during this initial phase, one protein stood out: IL-3. This molecule plays a central role in the early stage of the disease, when the central nervous system has already suffered significant damage even though patients do not yet experience symptoms. IL-3 helps recruit immune cells to the brain and spinal cord, where they begin attacking nerve tissue.
“We believe our work opens many opportunities to diagnose, monitor, and potentially treat MS,” said Ahmed Abdelhak, MD, assistant professor of neurology at the University of California, San Francisco, and first author and co-first author of the study published in the journal MS. Natural medicine On October 20th. “It could be a game-changer in how we understand and manage this disease.”
Follow up on blood evidence years before diagnosis
The researchers analyzed more than 5,000 different proteins in blood samples taken from 134 individuals who eventually developed MS. These samples came from the US Department of Defense Serum Repository, which stores blood from military applicants. Because the repository holds samples for decades, scientists were able to examine blood taken years before these individuals were diagnosed.
Seven years before diagnosis, researchers detected an elevation in a protein known as MOG (myelin oligodendrocyte glycoprotein), which indicates damage to the myelin insulation around nerve fibers. About a year later, they noticed an increase in the nerve filament light chain, a sign that the nerve fibers themselves were injured.
During this same window, IL-3 and several related immune proteins appeared in the bloodstream, indicating that the immune attack was already underway.
Building the foundation for predictive blood testing
In total, the team identified about 50 proteins that could serve as early indicators of MS. They have since filed a patent application for a diagnostic blood test based on the 21 most reliable markers.
The findings could reshape how doctors approach prevention and treatment, said Ari Green, MD, chief of neuroimmunology and glial biology in the UCSF Department of Neurology and senior author of the study.
“We now know that MS begins much earlier than its clinical onset, creating the real possibility that one day we can prevent MS – or at least use our understanding to protect people from further infections.”
Authors: Other UCSF authors are Gabrielle Serono, MD, Chiara Ning, John Buscardin, PhD, UCSF Origins Study, Christian Cordano, MD, PhD, Asritha Toubati, Camille Voisier, Eric de Chao, PhD, Refugia Gomez, Adam Santaniello, Kelsey C. Zorn, MHS, Jill A. Ph.D., MPH, Jorge R. Oxenberg, MD, Bruce A.C. Cree, MD, PhD, MA, Steven L. Hauser, MD, Jonah R. Chan, MD, Sergio E. Baranzini, MD, Michael R. Wilson, MD, and Ari J. Green, MD. For all authors, see the paper.
Funding: This work was funded in part by the Department of Defense (HT94252310499), the National Institutes of Health (R01 NS105741 R01AG062562 R01AG038791, 1S10OD028511-01, R35NS111644), the Valhalla Foundation, the National MS Society, the Westridge Foundation, the National Multinational Foundation. Sclerosis Association (RFA-2104-37504, SI-2001-35751), the Water Cove Charitable Foundation, Tim and Laura O’Shaughnessy, and the Littera family. For all financing and disclosures, see the paper.
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