October 17, 2018
Emerging evidence points to a leaky blood-brain barrier as an early event that may lead to the death of nerve cells in multiple sclerosis. Until now, treatments to inhibit the blood from harming the brain were not available. Scientists from the Gladstone Institutes may have developed an antibody that blocks the inflammatory and oxidative activity of fibrin, which contributes to neurodegeneration in the brain. Using this approach, researchers could be in a position to achieve neuroprotection without shutting down protective immune responses or blood clotting.Normally, the blood protein fibrin does not enter the brain. But in several neurological disorders, the blood-brain barrier — which keeps large molecules in the blood from entering the brain — becomes abnormally permeable, allowing fibrin to leak into the brain and trigger inflammation. Researchers have shied away from targeting fibrin to treat neurological diseases because of concerns that targeting the protein would impair its beneficial role in blood clotting.To come up with a very precise and highly effective antibody, researchers focused on targeting only a small region of the fibrin protein involved in activating the immune system in the brain. This way, they avoided interfering with the part of the protein responsible for clotting. The therapeutic fibrin antibody entered the brain, accumulated at fibrin-rich areas, and protected against neuroinflammation and neurodegeneration. The study’s authors found treatment with the antibody reduced activation of inflammatory cells and their accumulation at sites of inflammation in the mouse model of MS. In addition, it reduced the loss of nerve axons.Results of mouse model studies sometimes do not translate to humans and may be years away from being a marketable treatment. However, the researchers said the next step will be to make a version of the antibody that can be used in human patients. Given that the treatment targets an immune response and a blood clotting factor, the authors caution that tests monitoring the immune system and blood clotting will be important during clinical evaluation.The findings were published in the journal Nature Immunology.
Emerging evidence points to a leaky blood-brain barrier as an early event that may lead to the death of nerve cells in multiple sclerosis. Until now, treatments to inhibit the blood from harming the brain were not available. Scientists from the Gladstone Institutes may have developed an antibody that blocks the inflammatory and oxidative activity of fibrin, which contributes to neurodegeneration in the brain. Using this approach, researchers could be in a position to achieve neuroprotection without shutting down protective immune responses or blood clotting.Normally, the blood protein fibrin does not enter the brain. But in several neurological disorders, the blood-brain barrier — which keeps large molecules in the blood from entering the brain — becomes abnormally permeable, allowing fibrin to leak into the brain and trigger inflammation. Researchers have shied away from targeting fibrin to treat neurological diseases because of concerns that targeting the protein would impair its beneficial role in blood clotting.To come up with a very precise and highly effective antibody, researchers focused on targeting only a small region of the fibrin protein involved in activating the immune system in the brain. This way, they avoided interfering with the part of the protein responsible for clotting. The therapeutic fibrin antibody entered the brain, accumulated at fibrin-rich areas, and protected against neuroinflammation and neurodegeneration. The study’s authors found treatment with the antibody reduced activation of inflammatory cells and their accumulation at sites of inflammation in the mouse model of MS. In addition, it reduced the loss of nerve axons.Results of mouse model studies sometimes do not translate to humans and may be years away from being a marketable treatment. However, the researchers said the next step will be to make a version of the antibody that can be used in human patients. Given that the treatment targets an immune response and a blood clotting factor, the authors caution that tests monitoring the immune system and blood clotting will be important during clinical evaluation.The findings were published in the journal Nature Immunology.
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