Targeting Blood-clotting Protein Can Restore Brain’s Potential to Repair Myelin Layer, Study Shows

A blood-clotting protein called fibrinogen prevents myelin production and blocks the neuron remyelination repair process in mice, a study finds.

The study, “Fibrinogen Activates BMP Signaling in Oligodendrocyte Progenitor Cells and Inhibits Remyelination after Vascular Damage,” appeared in the journal Neuron. Its conclusions offer new insights and open new therapeutic avenues for multiple sclerosis (MS) and Alzheimer’s disease, among other illnesses.

One common feature of several neurological disorders is the loss of the myelin layer that normally surrounds neurons. Myelin is essential not only to protect the neurons but also to let them process and transmit the electric pulses they use to communicate with each other. When myelin is degraded, neurons can not work properly and they eventually die.

Scientists have tried to better understand what factors contribute to the demyelinating process and how to protect neurons from it.

Attempting to add new insights, a research team led by Katerina Akassoglou, senior investigator at Gladstone Institutes and professor of neurology at the University of California, San Francisco (UCSF), tested if the blood-clotting protein fibrinogen could be involved in MS.

“We thought it might be important to look instead at the toxic environment outside the cell, where blood proteins accumulate,” Akassoglou said in a press release. “We realized that targeting the blood protein fibrinogen could open up the possibility for new types of therapies to promote brain repair.”

In a previous study, the team showed that when fibrinogen crosses the brain-blood barrier it can induce autoimmune responses in the brain, similar to those involved in MS. In this new study, the team revealed that fibrinogen can do much more than that.

Indeed, the blood-clotting protein can work as a signaling protein and trigger signals that block development of oligodendrocytes, the cells that produce myelin. This not only stops myelin production but also prevents the brain from repairing and rebuilding the protective myelin layer that is destroyed during the autoimmune-inflammatory process.

“We found that fibrinogen stops adult stem cells from transforming into the mature cells that produce myelin,” said Dr. Mark Petersen, assistant adjunct professor of pediatrics at UCSF and the study’s lead author. “This blockade could be harmful for regeneration in the brain.”

Inhibition of fibrinogen signals in experimental cells and mice models showed it is possible to reverse the adverse effects of the protein and promote remyelination. These results further support the pursuit of strategies targeting fibrinogen to boost the brain’s regenerative potential.

“Repairing myelin by eliminating the toxic effects of vascular damage in the brain is a new frontier in disease therapeutics,” said Dr. Lennart Mucke, director of the Gladstone Institute of Neurological Disease and professor of neurology at UCSF. “This study could change the way we think about how to repair the brain.”