MS brain damage starts years before symptoms appear: Study
Findings on timeline of disease onset could open new avenues for treatment
Signs of myelin damage are detectable about one year before damage to nerve fibers is apparent and about seven years before the onset of multiple sclerosis (MS) symptoms, a new study reveals.
These findings shed new light on the timing of MS onset, and could open new avenues to treat the disease at very early stages or even prevent it altogether.
“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,” Ari Green, MD, senior author of the paper and chief of the Division of Neuroimmunology and Glial Biology in the University of California, San Francisco Department of Neurology, said in a university news story.
The study, “Myelin injury precedes axonal injury and symptomatic onset in multiple sclerosis,” was published in Nature Medicine.
Researchers analyzed data from military personnel
The myelin sheath is a fatty covering that wraps around nerve fibers and helps them send electrical signals, a bit like rubber insulation around a metal wire. In MS, inflammation in the nervous system damages myelin and injures axons — the long, wire-like nerve fibers that send electrical signals — ultimately leading to disease symptoms.
By the time MS is diagnosed, patients exhibit obvious signs of myelin and axonal damage. This has led to questions about the exact timing of when MS starts to damage the nervous system, relative to when symptoms become obvious.
To gain more insight into the timeline, scientists analyzed data from more than 100 people who developed MS after enrolling in the military. Through a Department of Defense repository, these patients had blood samples available from years before they developed the disease.
The analysis also included data from people who didn’t develop MS, as well as some MS patients from other databases.
Earliest detectable changes indicated myelin damage
Results showed that some of the earliest detectable changes were increases in a myelin protein called MOG, indicating signs of myelin damage. A spike in MOG was observed on average about seven years before symptom onset.
Signs of axon damage, as assessed by a spike in another protein called neurofilament light chain, tended to appear about a year later, or six years before symptom onset.
In turn, signs of damage to astrocytes, the star-shaped brain cells that help to support nerve function, didn’t become apparent until around the same time as MS symptoms manifested. This was assessed based on levels of another protein called GFAP.
We think our work opens numerous opportunities for diagnosing, monitoring, and [possibly] treating MS. It could be a [game changer] for how we understand and manage this disease.
These data offer a plausible timeline for how MS tends to develop in the years prior to symptom onset, which the researchers said could have important implications for how the disease is understood and managed.
“We think our work opens numerous opportunities for diagnosing, monitoring, and [possibly] treating MS,” said Ahmed Abdelhak, MD, first and co-lead author of the paper and an assistant professor of neurology at UCSF. “It could be a [game changer] for how we understand and manage this disease.”
In addition to markers of brain cell damage, the researchers noted that MS patients also showed marked elevations of an inflammatory signaling molecule called interleukin-3 (IL-3) in the years prior to onset.
These data “suggest a prominent role of IL-3 in the pathophysiology [disease biology] of MS in the early stage of the biological initiation of the disease,” the researchers wrote.
Finally, the team explored whether some of the proteins that were different in patients compared with healthy controls could be used to detect MS in the presymptomatic stage. They found that a model using 21 of the proteins could accurately identify 79% of presymptomatic patients.
The scientists have submitted a patent application for a diagnostic blood test using these 21 proteins that could be used to detect MS even before symptoms manifest.
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