Research uncovers signs of brain damage years before MS diagnosis

MS may damage the brain for years before symptoms appear, new research has found.

Scientists have gained new insight by examining thousands of proteins circulating in the blood, providing the clearest picture so far of when the condition first attacks the myelin sheath, the protective layer that surrounds nerve fibres.

The results show that the immune system starts targeting nerve cells much earlier than previously believed.

The research was conducted by scientists at UC San Francisco.

Ahmed Abdelhak, assistant professor of neurology at UCSF and first and co-lead author of the study, said: “We think our work opens numerous opportunities for diagnosing, monitoring, and possibility treating MS. It could be a game-changer for how we understand and manage this disease.”

The researchers tracked fragments left behind by immune attacks in blood samples, along with molecular signals that guide immune cells to their targets. Together, these measurements allowed the team to map out the order of biological events that eventually lead to multiple sclerosis, something that had not been clearly defined before.

The findings show that the condition initially damages the fatty myelin sheath. About a year later, signs of injury to the nerve fibres themselves become detectable.

Among the many immune signalling proteins that rose early in the disease process, one stood out.

The protein IL-3 appears to play a key role during this silent stage, when the central nervous system is already experiencing significant damage, but patients still feel no symptoms. I

L-3 is known to draw immune cells into the brain and spinal cord, where they attack nerve cells.

To reach these conclusions, the researchers analysed more than 5,000 proteins in blood samples from 134 people with multiple sclerosis, collected both before and after diagnosis.

The samples came from the US Department of Defense Serum Repository, which stores blood samples from service members when they apply to join the military.

These samples can be studied decades later, after some individuals have gone on to develop the condition.

Seven years before diagnosis, researchers detected a sharp increase in a protein called MOG, which stands for myelin oligodendrocyte glycoprotein. This protein signals damage to the insulating layer around nerve fibres.

About one year after the MOG increase, levels of neurofilament light chain rose, indicating damage to the nerve fibres themselves. Neurofilament light chain is a protein released when nerve fibres are damaged.

During this same period, IL-3 and other immune-related proteins involved in directing immune responses also appeared in the blood.

Overall, the team identified roughly 50 proteins that signal an increased risk of developing the condition in the future. They have filed a patent application for a diagnostic blood test based on the 21 most promising markers.

Ari Green, chief of the Division of Neuroimmunology and Glial Biology in the UCSF Department of Neurology and senior author of the study, said the findings offer both hope for prevention and a clearer understanding of how symptoms eventually develop.

He said: “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.”