Fibrin is a blood protein that normally does not cross to the brain, however, several neurological disorders have a defect in the blood-brain barrier that allow large molecules, like fibrin, to pass through triggering inflammation. Many studies have pointed to a leaky blood-brain barrier as an early event in brain diseases that causes neurodegeneration. The process is believed to be implicated in the death of nerve cells seen in multiple sclerosis, Alzheimer's disease, and other disorders.
Treatments intended to inhibit the blood from harming the brain have not been available due to researchers fear of targeting the blood-clotting protein, fibrin, and the effect it may hold on bleeding patients. But, now, researchers from the Gladstone Institutes have found a way to overcome this hurdle with a new immunotherapy; a highly effective antibody that inhibits the biochemical activity of fibrin that contributes to neurodegeneration in the brain
"We have developed a monoclonal antibody to target a major culprit in the blood that damages the brain," said Katerina Akassoglou, PhD, lead investigator and a professor in the Department of Neurology at UC San Francisco. "Fibrin-targeting immunotherapy could protect the brain from the toxic effects of blood leakage and may also have beneficial effects in other organs affected by inflammatory conditions with vascular damage."
In a mouse model, the new antibody would enter the brain and accumulate in fibrin-rich regions, protecting against neuro-inflammation and neurodegeneration in both disease models. The research team published their findings in Nature Immunology. "We discovered that fibrin also contributes to brain disease through oxidative stress -- an unanticipated result," says research scientist and first author of the study, Jae Kyu Ryu, PhD. "Treatment with the antibody put a damper on this fibrin-driven oxidative mechanism, which may contribute to many different neurodegenerative diseases."
The study treated mouse models of Alzheimer’s with the antibody after they had developed an accumulation of amyloid proteins in their brain; a hallmark of the disease. In comparison, to the placebo, the mice had less brain inflammation and less neuronal death. "Our study supports that vascular damage leading to immune-driven neurodegeneration may be a common thread between diseases of different etiologies with blood-brain barrier leaks," said Akassoglou. "Targeting fibrin with immunotherapy is a new approach that could be used to test the therapeutic benefits of suppressing this pathogenic mechanism in multiple disease contexts."
Source: Gladstone Institute