Targeting Blood-clotting Protein Can Restore Brain’s Potential to Repair Myelin Layer, Study Shows
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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.”
T. Kierzek
Hi,
Reading your journal, i'am very eager to know what kind of fibinogenen were used on mice? Do you have the specific name , please
Thank you,
Alice Melão, MSc
They infused human fibrinogen in mice brains, at concentrations similar to those found in the plasma. To inhibit the effects of fibrinogen the researchers used a chemical inhibitor and genetically manipulated the mice so fibrinogen could not activate its signaling pathway on oligodendrocyte progenitor cells.
J Smyth
Mice and humans are different. To abuse animals is cruelty . SAD .
Alice Melão, MSc
Dear J Smyth,
Many ethical questions can be raised in science, and the use of animals is definitely one of them. Still for science to move forward, find new insights on diseases, and advance new potential therapies it is necessary to use models that can provide a good base of information. But is important to remind that all studies with animals have to pass the approval of ethical committees and they have to follow strict rules to ensure the animal do not suffer throughout all experimental procedures.
Frank J Campo Jr
If we can't use animals to test the efficacy of new drugs what would you like to use? How about using you for test trials?
Harvey Connors
Cruelty is people with your view trying to prevent people to find a cure so people don't have to suffer. Are you living with MS. I am. I will probably die from a bladder issue before any thing can help me. But I pray no one else has to suffer like me. I am great-full for this research.
frank
Animals are far less important to our life than the ability to live a disease-free life. Grow up.
Cecile
Please keep up the great research- we so do need a way to remyelinate when demyelination has happened with MS.
Coleen Sadewater
Is there a retrovirus in the faulty fibrinogen, and if so was another virus used to invade them to alter their distructive part? Also wouldn’t an anti-clotting drug stop it too? Thank you for your response!
Monica
How does this treatment effect clotting? Are the fibrinogen levels high enough to cause the risk of clots, strokes, PE? We treat MS with plasma pheresis with albumin which has a significant effect on fibrinogen levels has this been look at in relationship to your investigation?
huri tursan
I have always been against vivisection and having progressive MS since 30 years and observing scores of molecules tested on animals has not changed my respect for all creatures who have a nervous system and suffer pain. After billions of "animal models" are tortured so called scientists conclude that the findings may not be replicated in humans and either drop whatever has been an instrument of torture or pass to human testing in the form of clinical trials. In addition leaving aside the cruelty aspect true advances in medical science with a long lasting effect on the human condition have not come from animal testing.