Drug delivery breakthrough for Alzheimer’s disease

By Dr. Ananya Mandal, MDMar 21 2011

In a ray of hope for Alzheimer’s patients, researchers have developed a new way to deliver drugs directly to the brain.

Till date all attempts to get drugs into the brain were countered by the blood-brain barrier - the natural defense against potentially harmful chemicals floating around the body. However this new finding from a team from University of Oxford shows that now scientists have successfully switched off a gene implicated in Alzheimer’s disease in the brains of mice by exploiting tiny particles naturally released by cells, called exosomes.

These exosomes, injected into the blood, act as carriers of “drug vehicles” that can cross the impermeable blood-brain barrier to the brain where they are needed. The team at Oxford harvested exosomes from mouse dentritic cells, part of the immune system, which naturally produce large numbers of exosomes. They then fused the exosomes with targeting proteins from the rabies virus, which binds to acetylcholine receptors in brain cells, so the exosome would target the brain. They filled the exosomes with a piece of genetic code, siRNA, and injected them back into the mice. The siRNA was delivered to the brain cells and turned off a gene, BACE1, which is involved in Alzheimer's disease. The authors reported a 60% reduction in the gene's activity.

The study appeared in the journal Nature Biotechnology. Authors claim that the science is still at an early stage - and is many years from being tested in people. However they add that this could be applied to treat Parkinson’s disease, motor neurone disease and muscular dystrophy also.

According to lead scientist Dr Matthew Wood of Oxford's Department of Physiology, Anatomy and Genetics, “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…This is the first time this natural system has been exploited for drug delivery.” He explained that over years, “The major barrier for these drugs is delivery…This problem becomes even greater when you want to reach the brain. The blood-brain barrier - which stops most things in the blood stream from crossing to our brains - is much too great an obstacle…We’ve shown that a natural system could be exploited to deliver drugs across the blood-brain barrier. We believe we can use this same technology for Alzheimer’s, motor neurone disease, Parkinson’s and Huntington’s.” Safety tests would be needed before the technique could be used on people, he added. The team expects to start trials on humans in another five years.

Needless to add that the Alzheimer’s Society welcomed the findings but said more research was needed to see if the method would be effective. Dr Susanne Sorensen, head of research at the charity, said, “In this exciting study, researchers may have overcome a major barrier to the delivery of potential new drugs for many neurological diseases including Alzheimer’s…The blood-brain barrier protects the brain from harmful chemicals but also makes it difficult for drugs to reach the target cells. If this delivery method proves safe in humans, then we may see more effective drugs being made available for people with Alzheimer’s in the future.”

Dr Simon Ridley, head of research at Alzheimer's Research UK, said, “This is innovative research, but at such an early stage it’s still a long way from becoming a treatment for patients…Designing drugs that cross the blood brain barrier is a key goal of research that holds the promise of improving the effectiveness of Alzheimer's treatments in the future.”