Researchers have shown with high-resolution real-time photos of mice how nerves may be damaged during the early stages of multiple sclerosis. Multiple sclerosis, or MS, is an autoimmune disease. When a person has MS, the cells that normally protect the body against infection begin attacking the body’s nerve cells in the brain and spinal cord.
The research results suggest that the nerves may be damaged when fibrinogen, a blood-clotting protein, leaks into the central nervous system. This process activates microglia, which are the immune cells.
“We have shown that fibrinogen is the trigger,” said Katerina Akassoglou, Ph.D., an associate investigator at the Gladstone Institute for Neurological Disease and professor of neurology at the University of California.
With MS, immune cells destroy the protective sheath, known as myelin, that surrounds the nerves. The immune attack also causes leaks in the blood-brain barrier. This barrier keeps the brain from harmful substances in the blood. Eventually, this process causes nerve damage that can lead to problems with memory, vision, balance, coordination, and muscle strength.
Dr. Akassoglou has focused on the role of the blood-brain barrier leak in MS and has discovered that leakage of the blood-clotting protein fibrinogen can trigger brain inflammation,” said Ursula Utz, Ph.D., M.B.A., a program director at the National Institute of Health’s (NIH) National Institute of Neurological Disorders and Stroke (NINDS).
The technology that Dr. Akassoglou and her colleagues used is a cutting-edge image technique called two-photon laser scanning microscopy. It allowed them to take a close look at what happens in the animal model of MS.
“Our results provide the first evidence linking leakage of fibrinogen to neuronal damage,” said Dr. Akassoglou, “Vascular changes are the instigator of neurotoxicity.”
Basically, the leakage of fibrinogen and microglial activation occurred days before any signs of nerve damage appeared. This means that the problem begins in pre-clinical stages of the disease.
Current medications for MS are focused on suppressing autoimmunity, but the new study suggests that targeting the interaction between fibrinogen and microglia may be more effective.
“Current drugs target primarily downstream events. This interaction could be an upstream target that suppresses immunity and neurodegeneration,” said Dr. Akassoglou.
The exciting news here is that now that there are clues to how the MS nerve damage starts, they can focus on finding new ways to stop it before it begins!