The Power of Blood in Neurological Diseases: A New Approach to Understanding and Treating Alzheimer’s and More
The mystery of what causes complex neurological diseases like Alzheimer’s and multiple sclerosis has long perplexed scientists and doctors, presenting obstacles to early diagnosis and effective treatment. Even among identical twins who share the same genetic risk factors, one may develop a neurological disease while the other remains unaffected. This discrepancy is due to the intricate nature of neurological disorders, which are often linked to numerous rare genetic variants rather than a single gene.
Unlike diseases such as cystic fibrosis or sickle-cell anemia, where a single gene mutation is responsible for the condition, neurological diseases are influenced by a combination of genetic, environmental, and vascular factors. High blood pressure, aging, heart disease, obesity, and other vascular risks play a significant role in the development and progression of these complex diseases.
However, there is a common thread that ties most neurological diseases together, according to Dr. Katerina Akassoglou, a senior investigator at Gladstone Institutes: a toxic immune reaction triggered by blood leaking into the brain through damaged blood vessels. This revelation offers a new perspective on understanding and addressing neurological diseases that were previously thought to be unrelated conditions.
Akassoglou and her team’s research, detailed in a commentary article published in Cell’s 50th-anniversary “Focus on Neuroscience” issue, shed light on how blood leakage into the brain sets off a harmful immune response that damages neurons. One key protein, fibrin, typically involved in blood clotting, plays a central role in this cascade of events across various neurological conditions, including Alzheimer’s, traumatic brain injury, multiple sclerosis, premature birth, and even COVID-19.
The groundbreaking discovery made by Akassoglou’s lab involves neutralizing fibrin to deactivate its toxic properties and prevent the damaging effects caused by blood leakage in the brain. By developing a therapeutic monoclonal antibody that specifically targets fibrin’s inflammatory properties without impacting its role in blood coagulation, the team has shown promising results in protecting against and treating neurological diseases in animal models.
One of the most exciting advancements is the development of a fibrin-targeting immunotherapy that has demonstrated efficacy in animal models of multiple sclerosis, Alzheimer’s, and COVID-19 neurological effects. This therapy is currently undergoing Phase 1 safety clinical trials by Therini Bio, a biotech company dedicated to advancing discoveries from Akassoglou’s lab.
In their Cell commentary, Akassoglou and her collaborators advocate for a new era of brain research that integrates insights from immunologists, neuroscientists, hematologists, geneticists, computer scientists, physicists, bioengineers, drug developers, and clinical researchers. They emphasize the importance of interdisciplinary collaboration across academia, industry, and foundations to drive innovation in drug discovery and transform the medical landscape for neurological diseases.
With a focus on the immune and vascular systems’ critical roles in neurodegeneration, the researchers envision a future where scientific breakthroughs emerge from collaborative networks that leverage cutting-edge technologies and diverse expertise. This approach heralds a shift away from solely addressing genetic or environmental factors toward a more comprehensive understanding of the mechanisms driving neurological diseases.
As Dr. Akassoglou aptly summarizes, “To usher in this new era of drug discovery and treatment, we must embrace an interdisciplinary approach that acknowledges the interconnected nature of immune and vascular systems in neurodegenerative conditions.”
