Nanotechnology Isolates Brain Cell Derived Extracellular Vesicles from Blood, Demonstrating Clinical Utility through Serum Analysis of Patients with Brain Disorders

Asan Medical Center and Yonsei University Research Team Suggest Potential Biomarker for Monitoring Brain Changes without Repeated Imaging Tests

“We plan to further validate the findings in a large patient cohort to clarify the potential for clinical application.”

▲ (From left) Professor Eun-Jae Lee of Department of Neurology at Asan Medical Center, Dr. Jin Hee Kim of the Biomedical Research Center at Asan Institute for Life Sciences, Professor Shin Yong of the Department of Biotechnology at Yonsei University, and researchers Hyo Joo Lee and Yeonjeong Roh.

Most brain disorders progressively worsen over time, and damaged neurons rarely recover, making early diagnosis and continuous monitoring of disease activity essential. However, brain tissue biopsy is difficult to perform, and imaging tests such as MRI have limitations in precisely tracking subtle changes in disease status.

Recently, a Korean research team identified the potential for developing a new biomarker that can selectively detect signals from specific brain cells in the blood, enabling continuous monitoring of disease activity without the need for repeated imaging tests.

A research team led by Professor Eun-Jae Lee of Department of Neurology at Asan Medical Center, Dr. Jin Hee Kim of the Biomedical Research Center at Asan Institute for Life Sciences, Professor Shin Yong of the Department of Biotechnology at Yonsei University, and researchers Hyo Joo Lee and Yeonjeong Roh has developed a new nanotechnology that can selectively isolate and analyze signals derived from specific brain cells in the blood. The team recently reported that they successfully identified molecular changes that reflect disease activity.

The study is significant in that it demonstrated that signals derived from astrocytes in the brain and spinal cord can be analyzed through a low cost blood test, enabling evaluation of disease activity in brain disorders.

In the global medical community, efforts have been actively underway to develop blood based biomarkers that are minimally invasive and easily accessible. However, reliable indicators that can accurately predict disease recurrence or directly reflect disease activity have remained limited.

Recently, extracellular vesicles have attracted attention as a promising approach to overcome these limitations. Extracellular vesicles are tiny particles secreted by cells that carry a variety of biological information, including proteins and micro ribonucleic acids (miRNAs).

In particular, recent findings that brain derived extracellular vesicles can cross the blood brain barrier, which regulates the movement of substances between the brain and the bloodstream, and enter peripheral blood have led to growing research efforts aimed at detecting changes in the brain through blood samples. In addition, the contents of extracellular vesicles are protected from the external environment, allowing them to remain relatively stable.

However, because blood contains extracellular vesicles originating from various types of cells, it has been difficult to selectively isolate vesicles derived from a specific cell type.

To address this challenge, the research team developed Engineered Peptide Imprinted Nanocomposites (EPIN), which mimic the structure of specific proteins to precisely recognize target molecules. The technology is designed to recognize surface proteins of astrocytes, enabling selective isolation of astrocyte derived extracellular vesicles from the numerous vesicles present in blood. The isolation process can be completed within 40 minutes.

To evaluate the clinical applicability of the technology, the research team conducted analyses involving patients with neuromyelitis optica spectrum disorder. Neuromyelitis optica spectrum disorder is an autoimmune disease that repeatedly attacks astrocytes, leading to recurrent acute relapses and the accumulation of neurological disabilities. Therefore, accurately assessing disease activity is crucial for establishing appropriate treatment strategies.

The team performed a two stage clinical validation using 147 serum samples stored in the Asan Medical Center Biobank. First, they analyzed 108 serum samples obtained from patients who visited Asan Medical Center between 2019 and 2023. These included 39 samples from patients who had recently experienced an acute relapse, 49 samples from patients in a stable phase without acute symptoms, and 20 samples from healthy controls.

They then conducted an additional validation analysis using 39 samples collected from patients who visited between 2024 and 2025 to determine whether the method could distinguish the condition from other neurological disorders. The analysis included serum samples from patients with neuromyelitis optica spectrum disorder, as well as those with multiple sclerosis, Parkinson’s disease, and healthy controls.

The analysis showed that levels of glial fibrillary acidic protein (GFAP), a marker reflecting astrocyte damage, were higher in patients experiencing relapse than in those in a stable phase. In contrast, levels of aquaporin 4 immunoglobulin G (AQP4 IgG), an essential biomarker for diagnosing neuromyelitis optica spectrum disorder, tended to decrease in patients during relapse. Notably, AQP4 levels appeared independent of patients’ age or the degree of neurological disability, suggesting their potential as an indicator reflecting relapse status.

In addition, analyses including patients with other neurological disorders such as multiple sclerosis and Parkinson’s disease revealed distinct molecular patterns compared with neuromyelitis optica spectrum disorder, indicating the possibility of differentiating the disease from other conditions. Molecular signals that changed characteristically during relapse were also observed in micro ribonucleic acids contained within extracellular vesicles.

Professor Eun-Jae Lee of the Department of Neurology at Asan Medical Center said, “This study suggests the possibility of monitoring changes in the brain without repeated imaging tests. It is expected to be useful in predicting treatment responses and establishing personalized treatment strategies in the future. We plan to conduct further validation in a large patient cohort to clarify its potential for clinical application.”

Professor Shin Yong of the Department of Biotechnology at Yonsei University said, “The peptide imprinted nanocomposite technology is a platform technology that achieves molecular level selectivity by mimicking the structural characteristics of target proteins. It is particularly meaningful that the effectiveness of the technology was verified using serum from clinical patients, and we expect it to serve as a foundational technology that can be expanded to various brain disorders.”

Meanwhile, the study was supported by the Rare Disease Diagnosis Technology Development Program of the Korea Health Industry Development Institute and the Mid Career Researcher Program of the National Research Foundation of Korea. The findings were recently published in Nano Today, a leading international journal in nanoscience and nanotechnology (impact factor 10.9).