Beating the blood-brain barrier

The impermeable blood-brain barrier makes it impossible to deliver drugs to fight neurodegenerative diseases to the brain, but researchers have discovered a way through the wall – exosomes.

Exosomes are natural nanoparticles – small capsules produced by most cells in the body in varying amounts. They are thought to be a means of communication between different cells and the immune system. When they break away from the outer walls of cells they can carry cellular signals and genetic material, transporting the material between different cells.

It is this action which researchers from the University of Oxford have exploited to deliver gene therapy to mice suffering from Alzheimer’s disease.

“This is the first time this natural system has been exploited for drug delivery,” said Dr Matthew Wood from the department of physiology, anatomy and genetics.

Firstly, researchers produced and purified exosomes from mouse cells. Then they developed and patented new methods to insert RNA molecules into the exosome and add protein elements to the exosome coat that would target nerve cells. The exosomes were then injected intravenously into mice where they were shown to cross the blood-brain barrier.

Once in the brain, the RNA was able to switch off a gene implicated in the build up of malformed protein in Alzheimer’s. This resulted in a 60% decrease in the problem enzyme encoded by the gene in the mouse brain.

“These are dramatic and exciting results. It’s the first time new “biological” medicines have been delivered effectively across the blood-brain barrier to the brain,” Wood said. “We believe we can use this same technology for Alzheimer’s, motor neuron disease, Parkinson’s and Huntington’s. All we need is different RNA each time.”

Although this is a significant result, there are a number of additional steps that will need to be taken before the new form of drug delivery can be tested in humans in the clinic, including safety tests and scaling up the process.