Study shows infectious prions can arise spontaneously in normal brain tissue

[JBeukema]

In a startling new study that involved research on both sides of the Atlantic, scientists from The Scripps Research Institute in Florida and the University College London (UCL) Institute of Neurology in England have shown for the first time that abnormal prions, bits of infectious protein devoid of DNA or RNA that can cause fatal neurodegenerative disease, can suddenly erupt from healthy brain tissue.
The catalyst in the study was the metallic surface of simple steel wires. Previous research showed that prions bind readily to these types of surfaces and can initiate infection with remarkable efficiency. Surprisingly, according to the new research, wires coated with uninfected brain homogenate could also initiate prion disease in cell culture, which was transmissible to mice.
The findings are being published the week of July 26, 2010, in an advance, online edition of the journal Proceedings of the National Academy of Sciences (PNAS).

Study shows infectious prions can arise spontaneously in normal brain tissue

 

[waltky]

Medical mystery...

Boy Without a Cerebellum Baffles Doctors
Feb 12, 2011 – Heather and David Britton want everyone to understand a few things about their giggling, bespectacled 3-year-old son, Chase. "He's happy. We call him the Little Gremlin. He loves to play tricks on people. He loves to sing. His goal in life is to make people smile," Heather Britton told AOL News.

"He's got so much love around him. We're an extremely happy family. His story is not tragic." But to an outsider, the Brittons' story might seem heartbreaking. Another son, Trey, was born 11 weeks early and only expected to live moments. Instead, he died six weeks after his birth in 2008, on the same day he was scheduled to receive a liver transplant. Cleared to get pregnant again, the couple was thrilled when Chase was conceived, Britton said. They were eager to give older son Alex, 13, a sibling.

Chase was also born prematurely, and he was legally blind. When he was 1 year old, doctors did an MRI, expecting to find he had a mild case of cerebral palsy. Instead, they discovered he was completely missing his cerebellum -- the part of the brain that controls motor skills, balance and emotions. "That's when the doctor called and didn't know what to say to us," Britton said in a telephone interview. "No one had ever seen it before. And then we'd go to the neurologists and they'd say, 'That's impossible.' 'He has the MRI of a vegetable,' one of the doctors said to us."

Chase is not a vegetable, leaving doctors bewildered and experts rethinking what they thought they knew about the human brain. "There are some very bright, specialized people across the country and in Europe that have put their minds to this dilemma and are continuing to do so, and we haven't come up with an answer," Dr. Adre du Plessis, chief of Fetal and Transitional Medicine at Children's National Medical Center in Washington, D.C., told Fox News affiliate WGRZ. "So it is a mystery."

Chase also is missing his pons, the part of the brain stem that controls basic functions, such as sleeping and breathing. There is only fluid where the cerebellum and pons should be, Britton said. Britton's pregnancy was complicated, so doctors closely monitored her. Deepening the mystery, she has detailed ultrasound pictures of Chase's brain during various stages of fetal development and the images clearly show he once had a cerebellum. "That is actually a fundamental part of the dilemma," du Plessis told WGRZ. "If there was a cerebellum, what happened to it?"

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[Quantum Windbag]

In a startling new study that involved research on both sides of the Atlantic, scientists from The Scripps Research Institute in Florida and the University College London (UCL) Institute of Neurology in England have shown for the first time that abnormal prions, bits of infectious protein devoid of DNA or RNA that can cause fatal neurodegenerative disease, can suddenly erupt from healthy brain tissue.
The catalyst in the study was the metallic surface of simple steel wires. Previous research showed that prions bind readily to these types of surfaces and can initiate infection with remarkable efficiency. Surprisingly, according to the new research, wires coated with uninfected brain homogenate could also initiate prion disease in cell culture, which was transmissible to mice.
The findings are being published the week of July 26, 2010, in an advance, online edition of the journal Proceedings of the National Academy of Sciences (PNAS).

Study shows infectious prions can arise spontaneously in normal brain tissue

I hate to break the news to those guys, but normal brain tissue does not grow on steel wires.

 

[waltky]

Granny says sometimes Uncle Ferd's brain don't get the message...

Brain disorder 'messaging clue'
13 March 2011 - Nerve fibres are 'message highways'

Scientists say they have discovered a "maintenance" protein that helps keep nerve fibres that transmit messages in the brain operating smoothly. The University of Edinburgh team says the finding could improve understanding of disorders such as epilepsy, dementia, MS and stroke. In such neurodegenerative disorders, electrical impulses from the brain are disrupted.

This leads to an inability to control movement, and muscles wasting away. The brain works like an electrical circuit, sending impulses along nerve fibres in the same way that current is sent through wires. These fibres can measure up to a metre, but the area covered by the segment of nerve that controls transmission of messages is no bigger than the width of a human hair.

Signal failure

The scientists discovered that the protein Nfasc186 is crucial for maintaining the health and function of the segment of nerve fibres - called the axon initial segment (AIS) - that controls transmission of messages within the brain. They found that the AIS and the protein within it are important in ensuring the nerve impulse has the right properties to convey the message as it should.

Professor Peter Brophy, director of the University of Edinburgh's Centre for Neuroregeneration, said: "Knowing more about how signals in the brain work will help us better understand neurodegenerative disorders and why, when these illnesses strike, the brain can no longer send signals to parts of the body."

Dr Matthew Nolan, of the university's Centre for Integrative Physiology, said: "At any moment tens of thousands of electrical impulses are transmitting messages between nerve cells in our brains. "Identifying proteins that are critical for the precise initiation of these impulses will help unravel the complexities of how brains work and may lead to new insights into how brains evolved." The work was funded by the Wellcome Trust and the Medical Research Council.

BBC News - Brain disorder 'messaging clue'

 

[waltky]

Getting drugs to brain cells has hampered medical advances...

Breakthrough in delivering drugs to the brain
20 March 2011 - 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

 

[waltky]

Good use of animal trials...

Study shows possible breakthrough for cerebral palsy
18 Apr.`12 - A new treatment helped rabbits born with cerebral palsy regain near-normal mobility, offering hope of a potential breakthrough in treating humans with the incurable disorder, researchers said Wednesday.

The method, part of the growing field of nanomedicine, worked by delivering an anti-inflammatory drug directly into the damaged parts of the brain via tiny tree-like molecules known as dendrimers. Baby rabbits treated within six hours of birth showed "dramatic improvement in motor function" by the fifth day of life, said lead author Sujatha Kannan of the National Institute of Child Health and Human Development Perinatology Research Branch. The study appears in the journal Science Translational Medicine.

Rabbits who were born immobile due to cerebral palsy were moving around at "almost... normal healthy levels by day five," said an accompanying article in the same journal by Chicago pediatrician Sidhartha Tan. The drug was one that is commonly used to treat people who overdose on acetaminophen, known as N-acetyl-L-cystine or NAC, and was given at a 10 times smaller amount. However, it was successful because the nanodelivery method allowed it to cross the blood-brain barrier and swiftly shut down inflammation in the brain.

Kannan said her team used rabbits because, like humans, their brains develop some before birth and some after birth, whereas most other animals are born with their motor abilities already formed. "An advantage of that is we can test therapies and look at the improvement in motor function using this kind of animal model," she said.

While experts say it may be many years before it will be known if this approach can be used in human babies, the research shows an important proof of concept that some type of early intervention can reverse brain damage. "The importance of this work is that it indicates that there is a window in time, immediately after birth, when neuroinflammation can be identified and when treatment with a nanodevice can reverse the features of cerebral palsy," said co-author Roberto Romero, an obstetrician at the National Institute of Child Health and Human Development.

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[waltky]

When Alzheiner's strikes the young...

Early-onset Alzheimer's strikes families fast and ferociously
30 May 2012 - Alzheimer's is thought of as a disease of the elderly. But the early-onset form of the disease can wreak havoc for young people and their families.

On a fall day in Westbury, New York state, Brandon Henley, 18, hastily opens the front door of his small house. The nurse his mother has been calling all day has finally arrived to deliver urgently needed anti-seizure medicine. Behind him, she notices on a recliner a frail man, eyes closed, under many blankets. "Is that your grandfather?" she asks. "No, it's my father," says Henley. Mike Henley is 47. What hair he has left is white. He no longer has teeth and is so thin and pale that it seems he could vanish at any moment. He cannot speak, he cannot walk and no-one knows if he can understand what is going on around him. Mike Henley has Alzheimer's disease.

'What about the kids?'

When he was diagnosed at 36, doctors said he would die within five to seven years. More than a decade later he survives. "Younger people's bodies are stronger," says his wife, Karen. But young-onset Alzheimer's also progresses faster than the disease in older people. Mike was diagnosed in 2001. By 2004 he was unable to speak and by 2006 he was unable to walk. An estimated 5.4 million Americans have Alzheimer's. Early-onset Alzheimer's disease, commonly known as young-onset Alzheimer's disease, afflicts people under 65 and accounts for less than 10% of cases of the disease.

In the UK, the Alzheimer's Society provides statistics on all forms of dementia, noting that Alzheimer's accounts for the majority of these cases. They count 800,000 people with dementia in the UK, including more than 17,000 younger people. It is a small proportion, but an extremely aggressive form of the disease. The impact on patients and families is typically severe. Once diagnosed with Alzheimer's, younger people have scant time to organise their future. They face a lot of legal work: coping with insurers, arranging for Social Security and power of attorney.

Mike's first question, when he learned he had Alzheimer's, was "What are we going to do about the kids?" At the time, Courtney was nine years old and Brandon eight. At first Mike and Karen decided not to tell them anything, "but they were already questioning why he wasn't working anymore", recalls Karen. "I remember asking if mom and dad were going to get a divorce," says Courtney. "I kind of picked up on a difference to how things normally were going. That was the only thing that I knew could be wrong." With the help of a child psychologist, Karen started to explain to her children that their father had an illness affecting his brain. She said that he might say or do things that he wouldn't have before.

More BBC News - Early-onset Alzheimer's strikes families fast and ferociously

 

[waltky]

Granny says, "Lookit here what dey doin' at U of L!...

Researchers say Parkinson's cure may lie in the human nose
23 June`12 LOUIVILLE, Ky. – University of Louisville researchers hoping to find a cure for Parkinson's disease have discovered an unlikely potential treatment — stem cells from the human nose.

Videos from a laboratory at Louisville reveal the promise: One shows a rat with a brain damaged to mimic Parkinson's continually circling the bottom of a bowl in one direction, unable to do anything else. Another shows a similar rat injected with nasal stem cells moving normally and trying to climb out. The research — which uses an adult patient's own cells — is outlined in this month's issue of the journal Stem Cells Translational Medicine. "I think it would be wonderful to have thought of something … that could help people. That's what I'm in this for," said Louisville neuroscientist Fred Roisen, chief science officer and co-founder of a company based on the technology called RhinoCyte.

Parkinson's — which afflicts about a million Americans, including Louisville-born boxing legend Muhammad Ali— is a progressive neurological disorder that mostly strikes people over 50, causing tremors, slow movement and other problems. It occurs when nerve cells in the brain that produce dopamine, a chemical that helps control muscle movement, are slowly destroyed. It "is a terrible disease," Roisen said. "And as our population ages, there are gonna be more and more people with Parkinson's."

John Baumann, a 51-year-old Shelby County man diagnosed with it a decade ago, said he finds the research "interesting and coincidental" because his sense of smell was the first thing to go when he began developing Parkinson's. Loss of smell is considered an early warning sign. "Anything that could lead to a cure is wonderful news," said the lawyer, author and inspirational speaker. "Stem cells have always scared me, since there's so much opportunity for something to go wrong. But when it's done in a moralistic and disease-related way, I'm all for it."

Spurring improvement

Roisen said nasal stem cells are not a cure for Parkinson's but do seem to spur improvement in some research animals. The study says about 35% of rats getting the cells experienced "improved behavioral recovery." But Scott Whittemore, a stem cell researcher and vice chairman for research in the Department of Neurological Surgery at Louisville, pointed out that about two-thirds of the rats getting nasal stem cells didn't experience recovery. "This is an intriguing initial study," said Whittemore, who was not involved in the research. "But the success rate needs to be increased before it would be a potentially viable therapeutic option."

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[waltky]

Anti-Alzheimer's gene found...

Scientists find anti-Alzheimer's gene mutation
12 July`12 - Scientists have found a genetic mutation they say protects against Alzheimer's disease and holds promise for a possible treatment for this form of dementia.

More than five percent of people over the age of 60 in the Western world are believed to suffer from dementia, about two-thirds of which is due to Alzheimer's disease. Scientists in the United States and Europe reported in the journal Nature that they had found a gene coding mutation, A673T, that protects against both Alzheimer's and cognitive decline in elderly people who do not have the disease. "This is a mutation in a gene that makes a protein that people have believed for a long time is involved in Alzheimers," geneticist Kari Stefansson of the Icelandic medical company deCODE genetics and lead author of the paper, told AFP. "What this mutation does is to make the protein less harmful."

If you had the rare mutation, you were between five and seven times less likely to develop the disease than the general population, said Stefansson -- "a very strong protection". Probing the genetic data of some 1,800 Icelanders, the scientists also found that people between the ages of 80 and 100 who did not have Alzheimer's disease but carried the mutation had much better cognitive function than those without it.

He added there had been a lot of research in the past two decades into manipulating the amyloid precursor protein, APP, to treat Alzheimer's -- an incurable and progressive disease characterised by memory loss and dementia. The disease involves an accumulation of amyloid plaques in the brain. "This mutation could possibly represent a target for treatments to prevent Alzheimer's disease," a Nature press summary added.

Scientists find anti-Alzheimer's gene mutation - Yahoo! News

See also:

Alzheimer's 'early signs timeline developed'
11 July 2012 - Protein plaques in the brain indicate Alzheimer's disease

Scientists have assembled a "timeline" of the unseen progress of Alzheimer's before symptoms appear. A team at Washington University School of Medicine looked at families with a genetic risk of the disease. Writing in the New England Journal of Medicine, they say signs appeared up to 25 years before the expected onset of the disease. UK experts said the ability to detect Alzheimer's early would give the best chance of successful treatment.

'Key changes'

The 128 people in the study, from the UK, US and Australia, had a 50% chance of inheriting one of three mutations that are certain to cause early Alzheimer's, which often develops in people's 30s and 40s - much earlier than the more common form of Alzheimer's which generally affects people in their 60s. Those who carry the mutations will go on to develop the disease. The researchers looked at the age the participants' parents were when they developed the disease - and therefore how many years it was likely to be before they too showed symptoms. They underwent blood and spinal fluid tests as well as brain scans and mental ability assessments.

The earliest change - a drop in spinal fluid levels of the key ingredient of Alzheimer's brain plaques - can be detected 25 years before the anticipated age of disease onset, they suggest. At 15 years, raised levels of tau, a structural protein in brain cells can be seen in spinal fluid - and shrinkage can also be detected within parts of the brain. Changes in the brain's use of the sugar glucose and slight memory problems become apparent 10 years before symptoms would appear, they suggest. Researchers also tested other members of the families without the inherited mutations - and found no changes in the markers they tested for.

Prof Clive Ballard, director of research at the Alzheimer's Society, said: "This important research highlights that key changes in the brain, linked to the inherited form of Alzheimer's disease, happen decades before symptoms show, which may have major implications for diagnosis and treatment in the future. "These findings are a good indicator that there may be key changes in the brain happening early in people who develop non-hereditary Alzheimer's disease, but we can't be sure. Further research into this complex condition is needed to confirm a definite link."

And Dr Eric Karran, director of Research at Alzheimer's Research UK, said: "These results from people with the inherited form of Alzheimer's seem to be very similar to the changes in the non-genetic, common form of the disease. "It's likely that any new treatment for Alzheimer's would need to be given early to have the best chance of success. "The ability to detect the very earliest stages of Alzheimer's would not only allow people to plan and access care and existing treatments far sooner, but would also enable new drugs to be trialled in the right people, at the right time."

http://www.bbc.co.uk/news/health-18796309

 

[waltky]

Granny likes munchin' popcorn whilst she watches her evenin' TV...

Popcorn ingredient linked to Alzheimer's
Aug. 8,`12 (UPI) -- Diacetyl, a flavoring used to produce the buttery flavor and aroma of microwave popcorn and other food, may be linked to Alzheimer's, U.S. researchers say.

Robert Vince, director of the Center for Drug Design at the University of Minnesota, and colleagues Swati More and Ashish Vartak said diacetyl has been the focus of research recently because it is linked to respiratory and other problems in workers at microwave popcorn and food-flavoring factories. In addition to microwave popcorn, diacetyl is used in margarines, snack foods, candy, baked goods, pet foods and other products such as beer or some chardonnay wine, the researchers said.

Vince's team said it realized that diacetyl has an architecture similar to a substance that makes beta-amyloid proteins clump together in the brain -- this clumping is the hallmark of Alzheimer's disease. The study, published in the journal Chemical Research in Toxicology, found diacetyl increased the level of beta-amyloid clumping. In addition, the study found at real-world occupational exposure levels, diacetyl also enhanced beta-amyloid's toxic effects on nerve cells growing in the laboratory.

Other laboratory experiments also showed diacetyl easily penetrated the "blood-brain barrier," which keeps many harmful substances from entering the brain, Vince said. "In light of the chronic exposure of industry workers to diacetyl, this study raises the troubling possibility of long-term neurological toxicity mediated by diacetyl," the researchers said in a statement.

Read more: Popcorn ingredient linked to Alzheimer's - UPI.com

 

[waltky]

Epilepsy in the developing world...

Epilepsy Burdens Developing Countries
October 02, 2012 - Developing countries are seeing rising rates of noncommunicable diseases such as diabetes, cancer and cardiovascular disease. But researchers say those countries already have a disproportionate number of epilepsy cases compared to richer nations.

Researchers say despite epilepsy being “one of the most cost-effective disorders to treat,” developing nations carry a “heavy burden.” Twice as many people with epilepsy live in low and middle income countries. The findings appear in The Lancet medical journal. Oxford University Psychiatry Professor Charles Newton is the lead author. He spends much of his time in Kenya and Tanzania in the Wellcome Trust programs. “Epilepsy is a condition in which there is an excessive neuronal or electrical discharge within the brain causing the person to develop abnormal movements or impaired consciousness or even in some cases abnormal sensations,” he said.

Epilepsy is an umbrella term for a condition that has many causes and can happen at any age. “It can be inherited. It can have other genetic causes. It can be cause by infections, birth trauma, head injury and even such things as stroke and brain tumors,” he said.

Newton said that in Africa birth trauma often results from poor obstetrical care. And brain infections can result from such diseases as bacterial meningitis and malaria, among others. The disease also takes many forms. “You can have people staring blankly into space very frequently during the day. People having funny sensations, such as hallucinations, or people who fall down completely unconscious, go stiff, and then start convulsing, shaking on the ground, often wetting themselves,” he said. Those with epilepsy can also have a much higher mortality rate. For example, a person having a seizure may become unconscious and be more vulnerable to falling, fires or work accidents.

Epilepsy is an age-old health problem. The Epilepsy Therapy Project says the Greek physician Hippocrates wrote the first book about it in 400 B.C. He attempted to dispel myths, describing it as a brain disorder. Despite that early insight, those with epilepsy have faced stigma and discrimination. The affliction, at times, has been described as being the result of witchcraft, not only in the past, but the present. Newtown said stigma and discrimination give people with epilepsy less of a chance of getting an education, a job or even getting married. Their families are also often shunned. He said it doesn’t have to be that way.

More Epilepsy Burdens Developing Countries

 

[waltky]

Uncle Ferd gonna start takin' aspirin so he don't go goofy like Granny...

Aspirin may 'slow elderly brain decline', study finds
4 October 2012 - Could taking an aspirin a day slow brain power decline?

An aspirin a day may slow brain decline in elderly women at high risk of cardiovascular disease, research finds. Around 500 at risk women, between the ages of 70 to 92, were tracked for five years - their mental capacity was tested at the start and end of the study. Those taking aspirin for the entire period saw their test scores fall much less than those who had not. The Swedish study is reported in the journal BMJ Open.

Dr Silke Kern, one of paper's authors, said: "Unlike other countries - Sweden is unique, it is not routine to treat women at high risk of heart disease and stroke with aspirin. This meant we had a good group for comparison." The women were tested using a mini mental state exam (MMSE) - this tests intellectual capacity and includes orientation questions like, "what is today's date?", "where are we today?" and visual-spatial tests like drawing two interlinking pentagons.

No self-medication

But the report found that while aspirin may slow changes in cognitive ability in women at high risk of a heart attack or stroke, it made no difference to the rate at which the women developed dementia - which was also examined for by a neuropsychiatrist. Dr Simon Ridley, head of research at Alzheimer's Research UK, said: "The results provide interesting insight into the importance of cardiovascular health on cognition, but we would urge people not to self-medicate with aspirin to try to stave off dementia.

"The study reports no benefit from aspirin on overall dementia rates in the group, and previous trials investigating the potential of drugs like aspirin for dementia have been negative." Dr Kern added: "We don't know the long term risks of taking routine aspirin. For examples ulcers and serious bleeds may outweigh the benefits we have seen. More work is needed. We will be following up the women in this study again in five years."

BBC News - Aspirin may 'slow elderly brain decline', study finds