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In a groundbreaking study, Brazilian researchers have successfully created the first cell atlas for focal cortical dysplasia (FCD), a malformation of the cerebral cortex that causes drug-resistant epilepsy, particularly in children and adolescents. The discovery has the potential to revolutionize treatment options for those suffering from this devastating condition.
Focal cortical dysplasia is responsible for up to 50% of epilepsy surgeries in young patients, and the seizures associated with the disorder can be severe, with some individuals experiencing between 40 and 50 seizures per day. These seizures often involve loss of consciousness and falls, and when medication fails, surgery is considered, though it comes with risks such as vision, hearing, and speech problems.
The new cell atlas, developed using cutting-edge single-cell sequencing technology, provides a detailed map of the various cell types present in the brain lesions of FCD patients. By identifying which cells are involved in the disease, researchers hope to pave the way for more targeted and effective treatments for this form of dysplasia.
The research team, led by computational biologist Diogo Veiga from the Brazilian Institute of Neuroscience and Neurotechnology (BRAINN) and the School of Medical Sciences at the State University of Campinas (FCM-UNICAMP), published their findings in the journal iScience. Their study revealed critical insights into the molecular and cellular changes occurring in the brains of FCD patients.
The research uncovered subpopulations of neurons, microglia, and astrocytes involved in the disease. Notably, a specific population of neurons, characterized by the expression of neurofilament (NEFM+), was found to include dysmorphic neurons—abnormal cells that cause the altered synapses leading to seizures. Additionally, two distinct subpopulations of microglia were identified, suggesting a role in immune activation and neuroinflammation.
Veiga and his team also discovered profound changes in the cortical structure of FCD patients, including the loss of neurons in the upper layers of the cortex and an expansion of microglia populations associated with inflammation.
“This detailed cellular view is essential for understanding the mechanisms behind FCD and exploring potential therapies,” said Veiga. “By identifying these specific cell types, we are one step closer to developing targeted treatments.”
The study was a significant feat, as the researchers analyzed over 61,000 single cells from clinical samples of FCD lesions. This immense dataset was generated using single-cell sequencing, a technique that allows for the individual analysis of genetic material, providing a more granular understanding of cellular heterogeneity and the underlying pathology.
While the team’s findings mark a major advancement, Veiga notes that analyzing such large datasets presented challenges, requiring the development of specialized computational workflows. The research also benefited from the contributions of Ph.D. student Isabella Cotta Galvão, the first author of the study.
The research team shared their results at several national and international events, including the Human Cell Atlas Latin America Symposium in July 2024, and the workshop Single-Cell Omic Fusion: Navigating Spatial Omics in Biomedical Research in November 2024, aimed at fostering collaboration in the field.
Epilepsy affects an estimated 50 million people worldwide, and approximately 2 million people in Brazil alone. The new cell atlas adds to a growing body of knowledge about the genetic and molecular underpinnings of the disease. Last year, a major study identified 26 areas of the genome associated with epilepsy, and Brazil was the only Latin American country to contribute to that research.
The data generated by this study has been incorporated into the CellxGene cell database, part of the Human Cell Atlas Consortium, allowing other researchers worldwide to use it in the search for targeted treatments for FCD.
“The sharing of data generated with public funding is crucial to accelerate medical research,” said researcher Iscia Lopes-Cendes. “By making this data available, we’re ensuring that society’s investment in science can benefit everyone.”
Looking ahead, Veiga and his team plan to apply the same single-cell techniques to study infant brain development and explore other forms of dysplasia to identify possible similarities and deepen our understanding of neurological disorders.
Disclaimer: The information contained in this article is for general informational purposes only and is not intended as medical advice. Always consult with a healthcare professional for medical concerns.
