HKBU Researchers Engineer Exosomes to Deliver Alzheimer's Drug Across Blood-Brain Barrier
核心洞察
Hong Kong Baptist University researchers developed engineered exosomes to deliver Corynoxine-B (搜索), a compound from Chinese herbal medicine Gouteng, directly to the brain for Alzheimer's disease treatment.
The novel drug delivery system achieved a 30% reduction in accumulated amyloid-beta protein and 25% recovery of cognitive and locomotor behavior in mice with Alzheimer's disease.
The engineered exosomes successfully crossed the blood-brain barrier by overexpressing Fe65 (搜索) protein, which specifically targets neuronal cells with elevated amyloid-beta precursor protein levels.
A research team led by Hong Kong Baptist University (HKBU) has developed a breakthrough drug delivery system that uses engineered exosomes to transport a Chinese herbal compound directly to the brain for Alzheimer's disease treatment. The novel approach successfully overcame the blood-brain barrier challenge that has limited the therapeutic potential of Corynoxine-B (搜索), a bioactive compound extracted from the traditional Chinese medicine Gouteng.
The research findings, published in Nature-Signal Transduction and Targeted Therapy, demonstrate significant therapeutic improvements in mouse models of Alzheimer's disease, including a 30% reduction in accumulated amyloid-beta protein and 25% recovery of cognitive and locomotor behavior.
Addressing Critical Treatment Gap
Alzheimer's disease affects more than 55 million people worldwide, with no curative treatments currently available. In Hong Kong alone, more than 100,000 elderly suffer from dementia, with projections indicating this number will soar to more than 330,000 by 2039. The disease is characterized by brain cell degeneration and death, with a build-up of amyloid-beta and phospho-tau proteins leading to cognitive decline.
Previous HKBU research identified Corynoxine-B (搜索) as an effective compound for treating Alzheimer's disease. However, the blood-brain barrier, which protects the brain from potentially harmful substances in the bloodstream, significantly limited its therapeutic uptake in brain tissue.
Engineering Targeted Drug Delivery
The research team, comprising Professor Li Min, Associate Dean (Teaching and Learning) of Chinese Medicine, and Dr Ashok Iyaswamy, Research Assistant Professor at HKBU's School of Chinese Medicine, along with local, mainland and overseas scientists, developed a sophisticated approach using exosomes as drug carriers.
Exosomes are extracellular vesicles released by cells that can transport molecules between cells like nanocarriers. The researchers manipulated neuronal cells in mice to overexpress an adaptor protein called Fe65 (搜索) on the surface of exosomes. Fe65 plays a crucial role in processing amyloid-beta precursor protein (APP), which is central to Alzheimer's disease development.
The engineered exosomes containing Fe65 (搜索) demonstrated enhanced ability to migrate toward neuronal cells with overexpressed APP in Alzheimer's disease models. This targeting mechanism allows the exosomes to specifically interact with neuronal cells exhibiting elevated APP levels, a characteristic feature of Alzheimer's disease.
Therapeutic Efficacy and Autophagy Enhancement
Corynoxine-B (搜索) functions as a natural inducer of autophagy, a cellular process crucial for maintaining neuronal health. When loaded into the engineered exosomes and injected into mice with Alzheimer's disease, the system demonstrated remarkable therapeutic potential.
The engineered exosomes successfully crossed the blood-brain barrier to deliver Corynoxine-B (搜索) directly to brain tissue, resulting in enhanced autophagy in mice. Comprehensive behavioral testing, including rotarod tests, open field tests, contextual fear conditioning tests, and Morris's water maze tests, confirmed the therapeutic benefits.
Clinical Implications and Future Prospects
Professor Li Min emphasized the significance of the findings: "Our study suggests that exosomes could be a promising new way to deliver drugs to the brain and treat AD. More research is needed, but this study provides hope that a cure for AD may be possible in the future. We hope that this research project will ultimately be beneficial to the elderly, individuals at high risk of neurodegeneration and neurodegenerative disease patients."
The research represents a significant advancement in addressing one of the most challenging aspects of neurological drug development – effective delivery across the blood-brain barrier. The engineered exosome platform could potentially be adapted for other neurological conditions and therapeutic compounds, expanding its clinical applications beyond Alzheimer's disease treatment.