A research team at Seoul National University Hospital (SNUH) has identified a novel blood-based biomarker capable of enabling early diagnosis and treatment prediction in children with moyamoya disease, a rare cerebrovascular disorder that can lead to childhood stroke.
Moyamoya disease is a chronic, progressive cerebrovascular disorder characterized by the narrowing of the internal carotid arteries at the base of the brain without a known cause. This reduced blood flow triggers the formation of fragile, abnormal collateral vessels, which fail to provide adequate perfusion and are prone to rupture, leading to ischemic or hemorrhagic strokes in children.
While cerebral angiography currently remains the gold standard for definitive diagnosis,its invasive nature poses significant burdens for pediatric patients.
Non-invasive imaging such as MRI/A can be used but often overestimates vascular stenosis and lacks precision in evaluating the small moyamoya vessels at the brain’s base, underscoring the need for less invasive diagnostic alternatives such as liquid biopsy.
As a result, the team, led by Professor Kim Seung-ki of the Department of Pediatric Neurosurgery at SNUH, Koh Eun-jung of JLK Inc., and Research Professor Choi Seung-ah of the SNUH Kun-hee Lee Child Cancer & Rare Disease Project, discovered a new microRNA (miRNA) biomarker, miR-512-3p, in the blood plasma of pediatric patients with moyamoya disease and elucidated its functional mechanism.
The researchers analyzed extracellular vesicles (EVs) from the blood of 23 pediatric moyamoya patients and 13 healthy controls and identified miR-512-3p as a biomarker significantly elevated in patients compared with controls. EVs are nano-sized particles secreted by cells that carry genetic material, including miRNAs, and play a critical role in intercellular communication.
Further experiments revealed that miR-512-3p disrupts normal angiogenesis by targeting the RHOA signaling pathway, specifically suppressing the expression of the ARHGEF3 gene, thereby impeding vascular formation.
Notably, inhibition of miR-512-3p restored ARHGEF3 expression, increased GTPase activity by 2.3-fold, and enhanced the angiogenic potential of endothelial colony-forming cells (ECFCs) by 1.7-fold, indicating that targeting miR-512-3p could help normalize vascular development.
The biomarker demonstrated strong diagnostic accuracy with an area under the curve (AUC) of 0.82, highlighting its potential for early detection of moyamoya disease through a simple blood test.
The findings also suggested that miR-512-3p could serve as a therapeutic target, offering a dual role in both diagnosis and personalized treatment strategies.
“This study proves that moyamoya disease can be diagnosed early through a blood test,” Professor Kim said. “We expect that using this biomarker will allow pediatric patients to receive earlier diagnoses and benefit from tailored treatment approaches.”
The team has also secured a patent for the diagnostic application of miR-512-3p and a therapeutic screening method utilizing the ARHGEF3 gene in Korea.
The research, funded by the National Research Foundation of Korea, Seoul National University Hospital Research Fund, and the SNUH Kun-hee Lee Child Cancer & Rare Disease Project, was published in the latest issue of Scientific Reports.