New Insights into Neurological Disease Development
Neurological diseases like Alzheimer’s and multiple sclerosis (MS) have long puzzled researchers and medical professionals. Unlike simpler genetic disorders such as cystic fibrosis or sickle cell anemia, which are caused by a single gene, these neurological conditions are linked to hundreds of rare genetic variations. However, even individuals with the same genetic risk factors, like identical twins, don’t always develop the same disease. Environmental factors, aging, vascular risks, and lifestyle-related conditions such as high blood pressure, obesity, and heart disease further complicate the prediction of who will eventually suffer from these diseases.
According to Katerina Akassoglou, PhD, a senior investigator at Gladstone Institutes, there is a common but often overlooked factor linking many neurological diseases: blood leaks in the brain caused by damaged blood vessels. In these cases, blood proteins that typically do not enter the brain can set off harmful immune reactions. Akassoglou suggests that these immune responses triggered by blood entering the brain could be central to the development of conditions like Alzheimer’s and multiple sclerosis. She and her collaborators recently discussed these insights in a commentary published in Cell’s “Focus on Neuroscience” issue, marking the publication’s 50th anniversary.
Neutralizing Fibrin: A Potential Treatment
Akassoglou’s research focuses on how blood leaks in the brain can trigger neurological diseases. One of the key players in this process is a blood protein called fibrin, which normally helps with blood clotting. When it leaks into the brain, fibrin can activate the brain’s immune system in a harmful way, causing irreversible damage to neurons. This immune response has been observed in various conditions, including Alzheimer’s, MS, traumatic brain injuries, and even COVID-19.
Akassoglou and her team have discovered that by neutralizing fibrin, they can stop or prevent the damage it causes. This approach has been successful in animal models, where neutralizing fibrin protects the brain from damage caused by conditions like Alzheimer’s and multiple sclerosis. Her team developed a therapeutic monoclonal antibody that targets fibrin’s toxic effects without interfering with its essential role in blood coagulation. Early trials have shown promising results, with the treatment protecting against neurological damage in mice. The drug has now moved to Phase 1 safety clinical trials in humans, led by Therini Bio, a biotech company established to advance Akassoglou’s discoveries.
A New Approach to Neurological Disease Research
In their commentary, Akassoglou and her colleagues argue that neurological diseases like Alzheimer’s and multiple sclerosis, which have been traditionally viewed as separate conditions, must now be seen through a new lens. Their research highlights the important role that interactions between the brain, blood vessels, and the immune system play in these diseases. By focusing on the blood-brain-immune interface, researchers are uncovering a deeper understanding of how these diseases progress.
Looking forward, Akassoglou believes that significant scientific breakthroughs in treating neurological diseases will come from interdisciplinary collaboration. Researchers from fields such as immunology, neuroscience, hematology, genetics, and bioengineering will need to work together to push drug discovery beyond just addressing genetic or environmental factors. New technologies and approaches that account for the role of immune and vascular systems in neurodegeneration will be critical to the future of neurological disease treatment.
Akassoglou is optimistic that this evolving approach to research could lead to innovative treatments that protect against the devastating effects of neurological diseases. She emphasizes that by neutralizing the damaging effects of proteins like fibrin and by understanding the blood-brain-immune connection, researchers may be able to open a new chapter in treating complex neurological conditions.
