A groundbreaking study from researchers at Yale University and the Karolinska Institutet in Sweden has unveiled significant similarities between the molecular changes occurring during brain inflammation and those seen in normal neurodevelopment. This research could transform approaches to treating multiple sclerosis, an autoimmune disorder in which the immune system mistakenly attacks nerve cells in the brain.
The study, published on March 15, 2024, highlights the findings of a team led by Gonçalo Castelo-Branco, a prominent researcher at the Karolinska Institutet. In a recent interview, Castelo-Branco emphasized the importance of this basic research, stating, “With this kind of research, we understand better the property of the cells that are the major players in disease evolution.”
Innovative Mapping Techniques Uncover New Insights
The researchers built on existing technology that utilizes unique DNA barcodes to map the locations of molecules, such as RNA and proteins, within tissues. Traditional spatial technologies often measure only one property at a time. The team developed a new method termed “spatial tri-omic,” which allows for the simultaneous measurement of various properties, including gene activity, RNA expression, and protein production.
Through this innovative approach, the team analyzed both mouse brains and human brain tissue, revealing that shared patterns exist in the developmental processes of both species. Co-head of the study, Di Zhang, noted that microglial cells, which play a crucial role in brain development, also appear during neuroinflammatory processes. This suggests that the brain employs similar genetic and molecular mechanisms for development and self-repair following inflammation.
Zhang articulated the study’s significance in an email, stating, “In this study, we used spatial multi-omics to capture the brain’s journey of creation and self-healing — development, myelination, inflammation, and repair, not as separate chapters, but as movements of the same symphony of time.”
Implications for Multiple Sclerosis Treatment
The implications of this research extend beyond basic science, particularly in the realm of multiple sclerosis. Neuroinflammation can disrupt myelination, a critical process that protects nerve fibers and is essential for brain development and motor control. In multiple sclerosis, the immune system’s attack on the myelin sheath leads to chronic neuroinflammation and further damage.
Castelo-Branco explained that previous treatments for multiple sclerosis primarily targeted the immune system but were only effective during the early stages of the disease. The current research aims to provide insights for new medications that focus on the host tissue itself. “This is why these kinds of studies are important because then we can start understanding better how these molecules might be acting in the target tissue,” he said.
Zhang further highlighted the potential for developing improved therapeutic strategies and drugs for neuroinflammation and neurodegenerative diseases. She plans to expand the research to investigate other conditions, including Alzheimer’s and Parkinson’s diseases. Zhang also pointed out that this spatial technology could be applied to small tissue samples from various organs, such as the heart, lungs, and intestines, broadening the impact of their findings.
The Yale Department of Biomedical Engineering, established in 2003, continues to foster innovative research that bridges the gap between basic science and clinical applications, potentially paving the way for new treatment paradigms in neuroinflammatory and neurodegenerative diseases.