A new perspective on neurological diseases suggests that a toxic immune reaction, triggered by blood leaking into the brain, is a common factor in conditions like Alzheimer's and multiple sclerosis. Katerina Akassoglou, PhD, a senior investigator at Gladstone Institutes, emphasizes the importance of interactions between the brain, blood vessels, and the immune system in the progression of these diseases.
Neutralizing Fibrin: A Potential Therapeutic Strategy
Akassoglou's lab has focused on how blood leakage into the brain triggers neurological issues by activating the brain's immune system. Fibrin, a blood protein involved in coagulation, has been identified as a key culprit in this process, observed across various conditions, including Alzheimer's, traumatic brain injury, multiple sclerosis, premature birth, and COVID-19. The research indicates that neutralizing fibrin can prevent or interrupt this detrimental cascade, offering protection against multiple neurological diseases in animal models.
"As a first step, we know that neutralizing fibrin reduces the burden posed by vascular dysfunction," says Akassoglou. This approach appears protective regardless of the initial cause of blood leaks, such as head injury, autoimmunity, genetic mutations, brain amyloid, or infection.
Development of Fibrin-Targeting Immunotherapy
Scientists have developed a therapeutic monoclonal antibody that specifically targets the inflammatory properties of fibrin without affecting its role in blood coagulation. This fibrin-targeting immunotherapy has demonstrated protective effects in mice against multiple sclerosis and Alzheimer's, and has also shown promise in treating the neurological effects of COVID-19. Therini Bio, a biotech company, is currently conducting Phase 1 safety clinical trials for a humanized version of this immunotherapy.
A Collaborative Approach to Brain Research
In a commentary published in Cell, Akassoglou and her colleagues advocate for a shift in how neurological diseases are viewed, emphasizing the importance of the blood-brain-immune interface. They believe that future breakthroughs will emerge from collaborations between immunologists, neuroscientists, hematologists, geneticists, computer scientists, physicists, bioengineers, drug developers, and clinical researchers.
"This is a new opportunity for drug discovery that goes beyond addressing genes alone or environmental factors alone," Akassoglou states. She emphasizes the need to leverage new technologies and embrace an interdisciplinary approach that accounts for the roles of immune and vascular systems in neurodegeneration.
