HEALTH - Breakthrough in delivering drugs to thebrain

A new way of delivering drugs to the brain has been developed by
scientists at the University of Oxford.
They used the body's own transporters - exosomes - to deliver drugs in
an experiment on mice.
The authors say the study, in Nature Biotechnology , could be vital
for treating diseasessuch as Alzheimer's, Parkinson's and Muscular
Dystrophy.
The Alzheimer's Society said the study was"exciting" and could leadto
more effective treatments.
Research barrier
One of the medical challenges with diseases of the brain is getting
any treatment to cross the blood-brain barrier.
The barrier exists to protect the brain, preventing bacteria
fromcrossing over from the blood, while letting oxygen through.
However, this has also produced problems for medicine, as drugs can
also be blocked.
In this study the researchers used exosomes to cross that barrier.
Exosomes are like the body's own fleet of incredibly small vans,
transporting materials between cells.
Many potential drugs have not been properly tested because you
couldn't get enough of them into the brain"
Dr Susanne Sorensen
Alzheimer's Society
The team at Oxford harvested exosomes frommouse dentritic cells,
partof 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 inbrain 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.
"These are dramatic and exciting results" said the lead researcher Dr
Matthew Wood.
"This is the first time this natural system has been exploited for
drug delivery."
Customised
The research group believes that the method could modified to treat
other conditions and other parts of the body.
Dr Wood said: "We are working on sending exosomes to muscle, but you
can envisage targeting any tissue.
"It can also be made specific by changing the drug used."
The researchers are now going to test the treatment on mice with
Alzheimer's disease to seeif their condition changes.
The team expect to begintrials in human patients within five years.
Dr Susanne Sorensen, head of research at the Alzheimer's Society,
said:"In this exciting study, researchers may have overcome a major
barrierto the delivery of potential new drugs for many neurological
diseases including Alzheimer's.
She said the blood-brain barrier had been an"enormous issue as
manypotential drugs have not been properly tested because you couldn't
get enough of them into the brain."
She added: "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 isinnovative 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 theeffectiveness of
Alzheimer's treatments inthe future."
Exosomes may have othermedical applications.
Alexander Seifalian, a professor of nanotechnology and regenerative
medicine atUniversity College London, told the BBC:"Experimental
evidence indicates that exosomes can prime the immune system to
recognize and destroy cancer cells, making them a potential tool as
cancer vaccines."
He also said exosomes"could well form the cornerstone of nanoscaledrug
delivery systems of the future."
He added: "The apparent versatility and established biosafety of
exosomes underscores the potential of these biological membrane
vesicles to be of tremendous potential in the realm of nanotechnology
and regenerative medicine."