Breakthrough in delivering drugs to the brain

By James Gallagher

Health reporter, BBC News

 

Getting drugs to brain cells has hampered medical advances

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 diseases such as Alzheimer’s, Parkinson’s and Muscular Dystrophy.

The Alzheimer’s Society said the study was “exciting” and could lead to 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 from crossing 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.

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.

“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 see if their condition changes.

The team expect to begin trials 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 barrier to 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 many potential 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 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.”

Exosomes may have other medical applications.

Alexander Seifalian, a professor of nanotechnology and regenerative medicine at University 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 nanoscale drug 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.”

Reference Link : http://www.bbc.co.uk/news/health-12776222

Courtesy : BBC News

Singing 'rewires' damaged brain

By Victoria Gill Science reporter, BBC News, San Diego

Teaching stroke patients to sing “rewires” their brains, helping them recover their speech, say scientists.

By singing, patients use a different area of the brain from the area involved in speech.

If a person’s “speech centre” is damaged by a stroke, they can learn to use their “singing centre” instead.

Singing words made it easier for stroke patients to communicate

Researchers presented these findings at the annual meeting of the American Association for the Advancement of Science (AAAS) in San Diego.

An ongoing clinical trial, they said, has shown how the brain responds to this “melodic intonation therapy”.

Gottfried Schlaug, a neurology professor at Beth Israel Deaconess Medical Center and Harvard Medical School in Boston, US, led the trial.

The therapy is already established as a medical technique. Researchers first used it when it was discovered that stroke patients with brain damage that left them unable to speak were still able to sing.

Professor Schlaug explained that his was the first study to combine this therapy with brain imaging – “to show what is actually going on in the brain” as patients learn to sing their words.

Making connections

Most of the connections between brain areas that control movement and those that control hearing are on the left side of the brain.

“But there’s a sort of corresponding hole on the right side,” said Professor Schlaug.

“For some reason, it’s not as endowed with these connections, so the left side is used much more in speech.

“If you damage the left side, the right side has trouble [fulfilling that role].”

But as patients learn to put their words to melodies, the crucial connections form on the right side of their brains.

Previous brain imaging studies have shown that this “singing centre” is overdeveloped in the brains of professional singers.

During the therapy sessions, patients are taught to put their words to simple melodies.

Professor Schlaug said that after a single session, a stroke patients who was are not able to form any intelligible words learned to say the phrase “I am thirsty” by combining each syllable with the note of a melody.

The patients are also encouraged to tap out each syllable with their hands. Professor Schlaug said that this seemed to act as an “internal pace-maker” which made the therapy even more effective.

“Music might be an alternative medium to engage parts of the brain that are otherwise not engaged,” he said.

Brain sounds

Dr Aniruddh Patel from the Neurosciences Institute in San Diego, said the study was an example of the “explosion in research into music and the brain” over the last decade.

“People sometimes ask where in the brain music is processed and the answer is everywhere above the neck,” said Dr Patel.

“Music engages huge swathes of the brain – it’s not just lighting up a spot in the auditory cortex.”

Dr Nina Kraus, a neuroscientist from Northwestern University in Chicago, also studies the effects of music on the brain.

In her research, she records the brain’s response to music using electrodes on the scalp.

This work has enabled her to “play back” electrical activity from brain cells as they pick up sounds.

“Neurons work with electricity – so if you record the electricity from the brain you can play that back through speakers and hear how the brain deals with sounds,” she explained.

Dr Kraus has also discovered that musical training seems to enhance the ability to perform other tasks, such as reading.

She said that the insights into how the brain responds to music provided evidence that musical training was an important part of children’s education.

Reference Link: http://news.bbc.co.uk/2/hi/science/nature/8526699.stm

Courtesy : BBC News

Teen brain wired to take risks

Teenagers do crazy things, and the chemistry of their brains might explain why, say researchers.

The adolescent brain is extra sensitive to reward signals when pay-off for a risk is higher than expected, say cognitive neuroscientist Dr Russell Poldrack, from the University of Texas, Austin and colleagues.

They say the discovery might help explain why teens take risks that don’t seem worth it to adults – from driving too fast to experimenting with drugs.

“Teenagers seek out these sorts of rewarding experiences, and this provides a little explanation for that,” says Poldrack, whose research is published in this week’s Nature Neurosciece.

“In the long run, it may help us understand how addictions start and develop.”

Prediction error

To zero in on the neuroscience behind risk-taking behaviour in adolescents, Poldrack and colleagues focused on a concept called prediction error, which describes the difference between what a person expects to happen and what actually happens.

If you anticipate a rich sip of full-bodied espresso, for example, but you end up gulping weak, watery, and burnt coffee, that’s a negative prediction error.

If you expect nothing from a friend for your birthday but he gives you $20, that’s a positive error – far better than expected.

To test the brain’s reaction to positive prediction errors at different stages of life, the scientists enlisted 45 people, ranging in age from 8 to 30.

Each participant was shown a series of abstract kaleidoscopic images and challenged to categorise the figures as logos belonging to one of two fictional colleges.

When they got an answer right, participants earned a small amount of money and they all gradually learned which logos went with which colleges and which ones were worth more than others.

There were a few twists, though: Sometimes, an answer that should’ve been correct was judged as wrong.

Sometimes, a wrong answer was rewarded as a correct one. And sometimes, the reward was larger or smaller than the exercise indicated it should be.

With a mathematical model, the researchers were able to determine how much money each person expected to get with each answer and compare that with what they actually received. At the same time, fMRI’s showed what was happening in the brain.

Dopamine release

Previous research has shown a surge of activity in a brain region called the ventral striatum when reality exceeds a person’s expectations.

In the new study, the region’s response was highest in participants between 14 and 19 years old when they received more money than anticipated.

Brain activity in the ventral striatum is related to the release of dopamine, a nerve-signalling molecule that helps the brain process rewards and can be involved in addictions.

With more dopamine flowing, a teenager is likely to feel that a risky behaviour – when it ends well – is so much more rewarding than it might seem to a child or adult.

So, for example, the social rewards of staying out past curfew might outweigh the likelihood of getting in trouble for an adolescent.

And the physical pleasure of getting drunk might outweigh the dangers, including the next day’s hangover.

Besides providing insight into how addictions might begin in adolescence, the new study might help parents channel their teens into more positive risk-taking activities, like playing sports or acting in school plays, suggests Dr Adriana Galvan, a developmental cognitive neuroscientist at the University of California, Los Angeles.

“Adolescents are uniquely sensitive to the uncertainty in the world,” says Galvan. “Perhaps their willingness to engage in uncertainty is driven by the potential rewards that might result from that uncertainty. For them, the rewards loom so much bigger than the potential negatives.”

Reference Link
http://www.abc.net.au/science/articles/2010/05/18/2902619.htm?site=science&topic=latest

Courtesy
ABC