A research team led by Hong Kong Baptist University (HKBU) has developed a groundbreaking drug delivery system that successfully transports a Chinese herbal medicine compound across the blood-brain barrier to treat Alzheimer's disease. The innovative approach uses engineered exosomes to deliver Corynoxine-B, a bioactive compound from the traditional Chinese medicine Gouteng, directly to the brain of mice with Alzheimer's disease.
The research findings, published in Nature-Signal Transduction and Targeted Therapy, demonstrate significant therapeutic potential with a 30% reduction in accumulated amyloid-beta protein and 25% recovery of cognitive and locomotor behavior in treated mice.
Addressing Critical Treatment Gaps
Alzheimer's disease represents the most common type of dementia, characterized by brain cell degeneration and death due to amyloid-beta and phospho-tau protein buildup. Currently, more than 55 million people worldwide suffer from dementia, with over 100,000 elderly in Hong Kong affected by the condition. This number is anticipated to soar to more than 330,000 by 2039.
"At present there is no curative treatment for AD. Available treatments can only delay the disease's progression and improve symptoms," the researchers noted. While HKBU's previous research projects identified Corynoxine-B as effective in treating Alzheimer's disease, the blood-brain barrier posed a significant challenge to its uptake in the brain.
Engineered Exosome Technology
The research team, comprising Professor Li Min, Associate Dean (Teaching and Learning) of Chinese Medicine, and Dr Ashok Iyaswamy, Research Assistant Professor of the Teaching and Research Division at the School of Chinese Medicine at HKBU, developed a novel 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 Fe65 on the surface of exosomes released by these cells. Fe65 is involved in the processing of amyloid-beta precursor protein (APP), which plays a crucial role in Alzheimer's disease development.
The engineered exosomes showed enhanced ability to specifically target and interact with neuronal cells with elevated levels of APP, a characteristic feature of Alzheimer's disease. These findings suggest that the presence of Fe65 on the exosome surface improved their targeting capabilities.
Therapeutic Efficacy and Behavioral Improvements
Corynoxine-B functions as a natural inducer of autophagy, a 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 loaded with Corynoxine-B successfully crossed the blood-brain barrier to deliver the compound to the brain, resulting in a 30% reduction of accumulated amyloid-beta protein. The treatment enhanced autophagy in mice, supporting the maintenance of neuronal cell health.
Comprehensive behavioral testing, including the rotarod test, open field test, contextual fear conditioning test, and Morris's water maze test, revealed significant improvements in treated mice. The application of engineered exosomes loaded with Corynoxine-B resulted in 25% recovery of cognitive and locomotor behavior.
Future Implications
Professor Li Min emphasized the broader implications of this research: "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 successful development of this exosome-based delivery system represents a significant advancement in addressing the challenge of drug delivery across the blood-brain barrier, potentially opening new avenues for treating neurological disorders beyond Alzheimer's disease.
