Exosome-based drug delivery system for Alzheimer's treatment

An international team of researchers, led by Hong Kong Baptist University (HKBU), has developed a novel drug delivery system for treating Alzheimer’s disease (AD), with their results published in the journal Signal Transduction and Targeted Therapy.

AD is the most common type of dementia, in which the brain cells degenerate and die, resulting in the decline of the brain’s cognitive functions. At present there is no curative treatment for AD; available treatments can only delay the disease’s progression and improve symptoms.

HKBU’s previous research projects found that Corynoxine-B, a bioactive compound of the Chinese herbal medicine Gouteng, is effective in treating AD; however, the blood–brain barrier which protects the brain from potentially harmful substances in the bloodstream affects its uptake in the brain. To tackle this problem, researchers from HKBU and overseas have developed a novel approach to deliver Corynoxine-B to the brain using exosomes.

Exosomes are extracellular vesicles released by cells which can transport molecules between cells like nanocarriers. Recent studies have shown that they could be utilised as vehicles for drug delivery. To examine whether exosomes are effective drug carriers for AD, the researchers manipulated the 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 the development of AD.

By doing so, they observed more exosomes containing Fe65 were released by the neuronal cells. These engineered exosomes showed a good ability to migrate towards the neuronal cells with APP overexpressed in AD models. These findings suggest that the presence of Fe65 on the surface of exosomes enhanced their ability to specifically target and interact with the neuronal cells with elevated levels of APP, which is a characteristic feature of AD.

Corynoxine-B is a natural inducer of autophagy, a process that plays a crucial role in maintaining neuronal health. The research team loaded it into the engineered exosomes and injected it to the mice with AD to evaluate its potential as a therapeutic agent for the disease. Results show that engineered exosomes loaded with Corynoxine-B could enhance autophagy in mice, and were able to cross the blood–brain barrier to deliver Corynoxine-B to the brain, resulting in a 30% reduction of accumulated amyloid-beta protein.

In addition, various behavioural tests — including the rotarod test, open field test, contextual fear conditioning test and Morris’s water maze test — conducted on mice with AD showed that the application of engineered exosomes loaded with Corynoxine-B resulted in 25% recovery of the cognitive and locomotor behaviour. The new drug delivery system thus appears capable of improving cognitive function and movement while reducing the symptoms of AD.

“Our study suggests that exosomes could be a promising new way to deliver drugs to the brain and treat AD,” said Professor Li Min, Associate Dean (Teaching and Learning) of Chinese Medicine at HKBU. “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.”

Image caption: HKBU’s Professor Li Min and Dr Ashok Iyaswamy have developed a novel drug delivery system for Alzheimer’s disease treatment.