ScienceDaily
Wed, 30 Sep 2009
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Chaos brews in the brains of newborns: the nerve cells are still bound only loosely to each other. Under the leadership of Academy Research Fellow Sari Lauri, a team of researchers at the University of Helsinki has been studying for years how a neural network capable of processing information effectively is created out of chaos. The team has now found a new kind of mechanism that adjusts the functional development of nerve cell contacts.
The results were published in early September as the leading article of the Journal of Neuroscience.
The work carried out by Lauri's team and its partners at the Viikki campus sheds light on a development path that results in some of the large number of early synapses becoming stronger. The researchers found out hat the BDNF growth factor of nerve cells triggers a functional chain which promotes the release of the neurotransmitter glutamate. BDNF enables the release of glutamate by prohibiting the function of kainate receptors which slow down the development of the preforms of the synapses. The activity of the kainate receptors restricts the release of glutamate and the development of synapses into functional nerve cell contacts.
It is noteworthy that the brain of a newborn itself seems to organise its own development. The electrical activity of the waking brain triggers the series of events controlled by the BDNF protein, as a result of which kainate receptor activity disappears in some synapses. The development is based on the considerable plasticity of the developing neural network: it can reshape its structureand function to a large extent.
According to Lauri, the new research results help understand how central nervous system diseases originating in early development are established. The finding also provides researchers with the opportunity to obtain information about the different aspects of endogenous activity of the brain. At the same time, it could be possible to develop new kinds of pharmaceuticals for the treatment of childhood epilepsy, for example.
Lauri's team conducted the research in co-operation with the research teams of Eero Castren and Tomi Taira from the Neuroscience Centre, and the research team of Jari Yli-Kauhaluoma from the Faculty of Pharmacy.
vendredi 2 octobre 2009
mardi 22 septembre 2009
Scientists Make Paralyzed Rats Walk Again After Spinal-Cord Injury
Medical News Today
Mon, 21 Sep 2009
UCLA researchers have discovered that a combination of drugs, electrical stimulation and regular exercise can enable paralyzed rats to walk and even run again while supporting their full weight on a treadmill.
Published Nov. 20 in the online edition of Nature Neuroscience, the findings suggest that the regeneration of severed nerve fibers is not required for paraplegic rats to learn to walk again. The finding may hold implications for human rehabilitation after spinal cord injuries.
"The spinal cord contains nerve circuits that can generate rhythmic activity without input from the brain to drive the hind leg muscles in a way that resembles walking called 'stepping,'" explained principal investigator Reggie Edgerton, a professor of neurobiology and physiological sciences at the David Geffen School of Medicine at UCLA.
"Previous studies have tried to tap into this circuitry to help victims of spinal cord injury," he added. "While other researchers have elicited similar leg movements in people with complete spinal injuries, they have not achieved full weight-bearing and sustained stepping as we have in our study."
Edgerton's team tested rats with complete spinal injuries that left no voluntary movement in their hind legs. After setting the paralyzed rats on a moving treadmill belt, the scientists administered drugs that act on the neurotransmitter serotonin and applied low levels of electrical currents to the spinal cord below the point of injury.
The combination of stimulation and sensation derived from the rats' limbs moving on a treadmill belt triggered the spinal rhythm-generating circuitry and prompted walking motion in the rats' paralyzed hind legs.
Daily treadmill training over several weeks eventually enabled the rats to regain full weight-bearing walking, including backwards, sideways and at running speed. However, the injury still interrupted the brain's connection to the spinal cord-based rhythmic walking circuitry, leaving the rats unable to walk of their own accord.
Neuro-prosthetic devices may bridge human spinal cord injuries to some extent, however, so activating the spinal cord rhythmic circuitry as the UCLA team did may help in rehabilitation after spinal cord injuries.
The study was funded by the Christopher and Dana Reeve Foundation, Craig Nielsen Foundation, National Institute of Neurological Disorders and Stroke, U.S. Civilian Research and Development Foundation, International Paraplegic Foundation, Swiss National Science Foundation and the Russian Foundation for Basic Research Grants.
Mon, 21 Sep 2009
UCLA researchers have discovered that a combination of drugs, electrical stimulation and regular exercise can enable paralyzed rats to walk and even run again while supporting their full weight on a treadmill.
Published Nov. 20 in the online edition of Nature Neuroscience, the findings suggest that the regeneration of severed nerve fibers is not required for paraplegic rats to learn to walk again. The finding may hold implications for human rehabilitation after spinal cord injuries.
"The spinal cord contains nerve circuits that can generate rhythmic activity without input from the brain to drive the hind leg muscles in a way that resembles walking called 'stepping,'" explained principal investigator Reggie Edgerton, a professor of neurobiology and physiological sciences at the David Geffen School of Medicine at UCLA.
"Previous studies have tried to tap into this circuitry to help victims of spinal cord injury," he added. "While other researchers have elicited similar leg movements in people with complete spinal injuries, they have not achieved full weight-bearing and sustained stepping as we have in our study."
Edgerton's team tested rats with complete spinal injuries that left no voluntary movement in their hind legs. After setting the paralyzed rats on a moving treadmill belt, the scientists administered drugs that act on the neurotransmitter serotonin and applied low levels of electrical currents to the spinal cord below the point of injury.
The combination of stimulation and sensation derived from the rats' limbs moving on a treadmill belt triggered the spinal rhythm-generating circuitry and prompted walking motion in the rats' paralyzed hind legs.
Daily treadmill training over several weeks eventually enabled the rats to regain full weight-bearing walking, including backwards, sideways and at running speed. However, the injury still interrupted the brain's connection to the spinal cord-based rhythmic walking circuitry, leaving the rats unable to walk of their own accord.
Neuro-prosthetic devices may bridge human spinal cord injuries to some extent, however, so activating the spinal cord rhythmic circuitry as the UCLA team did may help in rehabilitation after spinal cord injuries.
The study was funded by the Christopher and Dana Reeve Foundation, Craig Nielsen Foundation, National Institute of Neurological Disorders and Stroke, U.S. Civilian Research and Development Foundation, International Paraplegic Foundation, Swiss National Science Foundation and the Russian Foundation for Basic Research Grants.
samedi 19 septembre 2009
Antioxidant Controls Spinal Cord Development
PhysOrg
Fri, 18 Sep 2009 13:55 UTC
Researchers at the Johns Hopkins School of Medicine have discovered how one antioxidant protein controls the activity of another protein, critical for the development of spinal cord neurons. The research, publishing this week in Cell, describes a never-before known mechanism of protein control.
"This is the first time we've seen this type of chemical reaction control neuronal differentiation," says Shanthini Sockanathan, Ph.D., an associate professor at the Johns Hopkins Solomon H. Snyder Department of Neuroscience. "And it's probably not specific for motor neurons that we study, but also for development of a wide variety of neurons."
Previous research had shown that the GDE2 protein can cause immature cells in the spinal cord to differentiate into motor neurons, the nerve cells that connect to and control muscle contraction. Too little GDE2 causes motor neurons to not develop, while too much GDE2 causes them to develop too quickly, depleting progenitor pools.
"We reasoned that there must be tight control of GDE2 so we set out to look for the regulator by looking for other proteins that can bind to GDE2," says Sockanathan.
Using biochemical approaches to isolate all proteins that normally bind to GDE2 in the developing spinal cord, followed by proteomic analysis to identify all binding proteins, the research team found a few hundred proteins. One, Prdx1, had been reported by others to have tumor-suppressing abilities, which caught Sockanathan's eye for further investigation.
The team first asked if the Prdx1 protein can affect motor neuron development by removing it from developing spinal cords of chick embryos. Embryos lacking Prdx1 showed loss of motor neurons similar to that seen in embryos lacking GDE2, suggesting that indeed Prdx1 is somehow involved in motor neuron development.
To figure out how Prdx1 and GDE2 interact to cause immature cells to develop into motor neurons, the team mutated the proteins and examined how the mutations affect the cells. Mutations that prevent the two proteins from binding resulted in no motor neurons. Similarly, mutations that disrupt the enzyme abilities of GDE2 and Prdx1 also resulted in no motor neurons. In fact, only when GDE2 and Prdx1 can bind each other and work as enzymes do motor neurons develop.
"So we thought maybe the antioxidant enzyme activity of Prdx1 is doing something to regulate GDE2 function," says Sockanathan. Her team then looked into what already was known about Prdx1's enzyme activity. They found that bacteria and yeast versions of Prdx1 are able to help alter certain chemical bonds in proteins that form between specific amino acids that contain so-called sulfhydryl or "-SH" groups.
That led them to reexamine the GDE2 protein for sulfhydryl groups. As it turns out, they found 4 in GDE2: Three are close together and one is clear on the other end of the protein. They first performed some biochemistry experiments to determine whether these sulfhydryl groups can form disulfide bonds - they can. Then, two at a time, the researchers engineered mutations to replace each -SH-containing amino acid in GDE2 and asked if the mutated protein could still bind to Prx1. They found one combination of mutations that did not behave the same as the unmutated control, leading them to conclude that Prx1 must break the chemical bond between those two specific amino acids.
"We think that Prx1 breaks this bond in GDE2, activating it to promote motor neuron differentiation," says Sockanathan. "This suggests a new general control mechanism that regulates when cells divide and when they differentiate. We're excited to see how widespread it might be."
Fri, 18 Sep 2009 13:55 UTC
Researchers at the Johns Hopkins School of Medicine have discovered how one antioxidant protein controls the activity of another protein, critical for the development of spinal cord neurons. The research, publishing this week in Cell, describes a never-before known mechanism of protein control.
"This is the first time we've seen this type of chemical reaction control neuronal differentiation," says Shanthini Sockanathan, Ph.D., an associate professor at the Johns Hopkins Solomon H. Snyder Department of Neuroscience. "And it's probably not specific for motor neurons that we study, but also for development of a wide variety of neurons."
Previous research had shown that the GDE2 protein can cause immature cells in the spinal cord to differentiate into motor neurons, the nerve cells that connect to and control muscle contraction. Too little GDE2 causes motor neurons to not develop, while too much GDE2 causes them to develop too quickly, depleting progenitor pools.
"We reasoned that there must be tight control of GDE2 so we set out to look for the regulator by looking for other proteins that can bind to GDE2," says Sockanathan.
Using biochemical approaches to isolate all proteins that normally bind to GDE2 in the developing spinal cord, followed by proteomic analysis to identify all binding proteins, the research team found a few hundred proteins. One, Prdx1, had been reported by others to have tumor-suppressing abilities, which caught Sockanathan's eye for further investigation.
The team first asked if the Prdx1 protein can affect motor neuron development by removing it from developing spinal cords of chick embryos. Embryos lacking Prdx1 showed loss of motor neurons similar to that seen in embryos lacking GDE2, suggesting that indeed Prdx1 is somehow involved in motor neuron development.
To figure out how Prdx1 and GDE2 interact to cause immature cells to develop into motor neurons, the team mutated the proteins and examined how the mutations affect the cells. Mutations that prevent the two proteins from binding resulted in no motor neurons. Similarly, mutations that disrupt the enzyme abilities of GDE2 and Prdx1 also resulted in no motor neurons. In fact, only when GDE2 and Prdx1 can bind each other and work as enzymes do motor neurons develop.
"So we thought maybe the antioxidant enzyme activity of Prdx1 is doing something to regulate GDE2 function," says Sockanathan. Her team then looked into what already was known about Prdx1's enzyme activity. They found that bacteria and yeast versions of Prdx1 are able to help alter certain chemical bonds in proteins that form between specific amino acids that contain so-called sulfhydryl or "-SH" groups.
That led them to reexamine the GDE2 protein for sulfhydryl groups. As it turns out, they found 4 in GDE2: Three are close together and one is clear on the other end of the protein. They first performed some biochemistry experiments to determine whether these sulfhydryl groups can form disulfide bonds - they can. Then, two at a time, the researchers engineered mutations to replace each -SH-containing amino acid in GDE2 and asked if the mutated protein could still bind to Prx1. They found one combination of mutations that did not behave the same as the unmutated control, leading them to conclude that Prx1 must break the chemical bond between those two specific amino acids.
"We think that Prx1 breaks this bond in GDE2, activating it to promote motor neuron differentiation," says Sockanathan. "This suggests a new general control mechanism that regulates when cells divide and when they differentiate. We're excited to see how widespread it might be."
Découverte de deux gènes qui aident à combattre la sclérose en plaque
ouest-france
01:04 - samedi 12 septembre 2009
Des chercheurs américains ont découvert deux gènes impliqués dans la restauration du système nerveux central de souris atteintes de sclérose en plaque. Cette découverte offre un nouvel espoir pour mettre au point des thérapies plus efficaces et prédire la façon dont les patients répondront à cette maladie auto-immune dégénérative.
L'équipe d'Allan Bieber, spécialiste des neurosciences à la clinique Mayo dans le Minnesota, a étudié des souris atteintes d'une forme chronique de maladie évolutive assimilée à la sclérose en plaque et a cartographié les gènes de celles qui ont spontanément réparé les dommages causés par la maladie. Les chercheurs ont découvert deux facteurs génétiques déterminants dans cette évolution positive
01:04 - samedi 12 septembre 2009
Des chercheurs américains ont découvert deux gènes impliqués dans la restauration du système nerveux central de souris atteintes de sclérose en plaque. Cette découverte offre un nouvel espoir pour mettre au point des thérapies plus efficaces et prédire la façon dont les patients répondront à cette maladie auto-immune dégénérative.
L'équipe d'Allan Bieber, spécialiste des neurosciences à la clinique Mayo dans le Minnesota, a étudié des souris atteintes d'une forme chronique de maladie évolutive assimilée à la sclérose en plaque et a cartographié les gènes de celles qui ont spontanément réparé les dommages causés par la maladie. Les chercheurs ont découvert deux facteurs génétiques déterminants dans cette évolution positive
mercredi 15 avril 2009
How PCBs May Hurt the Brain
New Studies Shed Light on Exposure to Environmental Toxin and Development of Brain Cells
Kathleen Doheny
WebMD Health News
April 13, 2009
Exposure to environmental toxins known as PCBs have long been linked with behavioral and developmental problems in children, but scientists could never say exactly how PCBs (polychlorinated biphenyls) might adversely affect the brain and lead to the problems.
Kathleen Doheny
WebMD Health News
April 13, 2009
Exposure to environmental toxins known as PCBs have long been linked with behavioral and developmental problems in children, but scientists could never say exactly how PCBs (polychlorinated biphenyls) might adversely affect the brain and lead to the problems.
Now, scientists think they may know.
The chemicals adversely affect the development of brain cells and also make brain circuits "overexcited," which has been linked in previous research to developmental problems, according to researcher Isaac N. Pessah, PhD, a professor of molecular biosciences and director of the University of California Davis Center for Children's Environmental Health.
"We think we have identified the way in which a broad class of environmental contaminants influences the developing nervous system and may contribute to neuro-developmental impairments such as hyperactivity, seizure disorders, and autism," says Pessah, a co-author on a trio of new studies examining the issue. The latest of the three is published online today in PLoS-Biology.
The findings of the three studies are called a "turning point" by another expert in the field.
One surprise finding: low levels of PCB exposure sometimes have greater ill effects than high-dose exposures.
PCBs were widely used for years in many products such as electronic components, pesticides, caulking, and flame retardants, but their production was banned in the U.S. in 1979.
Even so, the chemicals persist in the environment because they don't break down easily, explaining why high levels of PCBs can still be detected in people and in animals. PCBs are found in air, water, soil, and contaminated foods such as fish.
PCB Exposure and Effect on Learning and Brain Cells
In one of the three new studies, exposures to low doses of PCBs in animals hampered their ability to learn to swim a maze, a common test of animal learning.
The low PCB doses also adversely affected the plasticity of the animals' dendrites -- small projections branching out from the neurons or nerve cells that get signals from other cells in the body.
"This plasticity is very important for learning and memory," says study researcher Pamela Lein, PhD, associate professor of neurotoxicology at the UC Davis School of Veterinary Medicine.
The study was published in March in Environmental and Health Perspectives.
Problems in dendrite plasticity and growth have already been implicated in disorders such as autism, schizophrenia, and mental retardation, Lein says.
Lein and colleagues compared the effects of low-dose PCB exposure, high-dose exposure, and no exposure in three groups of rats that had been trained to swim and find an escape platform in a maze, and three groups not trained to swim the maze.
"The PCB treatments did affect the learning and memory," she says. "The effects were seen in the low-dose group but not the high-dose." Those in the low-dose trained group took longer to learn to swim and escape the maze, she says.
In the high-dose group, she says, the exposure may have triggered a compensatory mechanism that protected the brain cells from harm.
PCB Exposure: The Tissue Study
In a second study, the researchers looked at tissue from the animals' hippocampus, an area of the brain that regulates memory and emotion, and measured the "excitability" of neurons there before and during exposures to two different PCBs.
With one of them, says Pessah, "we can get an enhancement of excitability." Normally, information processing in the brain depends on a balance between excitation and inhibition of the neurons.
"Too much excitability is bad for the brain," Pessah says. Many neuro-developmental disorders, he says, including autism and attention deficit hyperactivity disorder or ADHD, "are thought to involve an imbalance between inhibition and excitability."
What they found in this study, he says, is that "even low levels [of PCBs] can tip the balance in the brain." The report is published in March in Toxicology and Applied Pharmacology.
PCB Exposure: The Cellular Level Clues
Finally, the researchers went to the cellular level, trying to find out more specifically how the PCBs change brain cell development as they found in the animal study and how they change the neurons' excitability, as seen in the study on brain tissue.
In the lab, they exposed receptors within the cells that regulate the release of calcium, crucial to maintain normal signaling from cell to cell, to PCBs. When they used electron microscope to create high-resolution images of the interaction between the receptors and the PCBs, they found the chemical binds to the receptors and adversely affects the calcium release. This interference accounts for the findings in the other two studies, Pessah says.
PCB Studies: Second Opinion
"I think that these studies represent a kind of a turning point for our recognition of how these chemicals, PCBs, can interfere with brain development," says R. Thomas Zoeller, PhD, professor of biology at the University of Massachusetts, Amherst. He was a journal reviewer for one study and reviewed the other two for WebMD.
"They are looking at a limited number of forms of PCB chemicals and they are linking exposures to very specific changes in proteins in the nervous system that impact brain development and behavior," he says. Because the animal model studied developmental events that are akin to human developmental events, ''for the first time we are getting a clear view of how these chemicals can impact the brain in humans," he says.
PCB Studies: Practical Applications
The new findings will add weight to the studies finding a link between exposures to PCBs and developmental problems, Lien says. "For the first time, we now have a plausible biological mechanism to explain the effect of PCBs on behavior."
One practical application of the research? Scientists may use the findings to evaluate the safety of numerous chemicals produced to take the place of PCBs, Zoeller says. "Science can't keep up with the rapid kinds of chemical changes that industry can manufacture," he says. "It would be great if we could get out in front of it and identify dangerous chemicals before people are being exposed."
The research findings may also make experts who thought lower-dose PCB exposures were not a problem think again, Pessah says.
mercredi 25 mars 2009
'Take control of your sleep, before it takes control of you'
Sify news
Monday, 23 March , 2009, 11:06
Monday, 23 March , 2009, 11:06
New Delhi: If you didn't sleep well last night or feel exhausted all day long, you are probably one of thousands suffering from sleeping disorders. It's possible that hypertension, acidity and several other lifestyle diseases are playing havoc with your sleep.
Good sleep helps you to be alert, awake and keeps you energetic throughout the day and hence a good night's sleep is vital for good health, experts say.
"As sleep is vital to our health and well-being, we must not cut ourselves short from the amount of sleep that we get or suffer from sleep problems. Take control of your sleep problems before it takes control of you," advised Ramnathan Iyer, a doctor who treats patients with sleep disorders.
A good night's sleep boosts immunity
Insomnia refers to the difficulty in initiation, maintenance, duration or quality of sleep. People may experience poor concentration, lower productivity and poorer work quality as a result of insomnia.
Sleep disorders can also make a person fatigued, irritable or forgetful and can lead to strained relationships.
Mumbai-based psychiatrist Manoj Bhatawadekar said: "To prevent or relieve sleep problems and safeguard sleep, making it more restful and pleasurable, it helps to practise good sleep hygiene."
Study links normal sleep and healthy ageing
A good 'sleep hygiene' would entail regular sleep or wake schedule, avoiding naps especially in the evenings, increase exercise, avoid intake of caffeine and alcohol just before sleeping, and schedule reasonable daytime work hours, Bhatawadekar said.
Many experts across the country from the Indian Sleep Disorders Association (ISDA) in association with Abbott India Limited, a health care company, have declared March 3 to April 7 as Sleep Awareness Month to generate awareness about the importance of sleep hygiene.
J C Suri, a doctor and president ISDA, said: "Sleep is important for mental, physical and emotional well-being."
Losing sleep? Blame it on long working hours
Iyer, who is ISDA's west regional governor, stressed: "Early assessment and action can prevent short-term sleep problems from developing into a chronic one."
Hypertension, arthritis, diabetes, acidity and some medications, including some heart medications, may even cause loss of sleep and stress.
When insomnia occurs in the context of chronic illness, it tends to be more severe than other forms of insomnia and usually involves sleep maintenance difficulties. A recent survey revealed that many lifestyle diseases also surfaced as a result of sleep disorders.
Sleep chemical eases brain disorders
Almost two-thirds of those surveyed reported the presence of at least one medical condition. These included 29 percent suffering from hypertension, 28 percent from arthritis, 19 percent coping with heartburn or gastroesophageal reflux disease, 18 percent battling depression, 11 percent dealing with diabetes, 10 percent with heart disease and 5 percent struggling with a lung disease. Obesity also was associated with a greater number of sleep-related problems.
People who reported a medical diagnosis were more likely than people without a diagnosis to sleep less than six hours per night on weekdays and experience symptoms of insomnia, the survey found.
lundi 9 mars 2009
Stem cells could save stroke victims
John von Radowitz
The Independent
Mon, 09 Mar 2009
Disabling strokes could one day be treated by replacing damaged brain tissue with stem cells, scientists have shown.
Researchers used a new technique to insert therapeutic stem cells into the brains of rats with pinpoint accuracy.
Once implanted the cells began to form new brain tissue and nerve connections.
The work is at an early stage and does not yet prove that stroke symptoms such as paralysis can be reversed.
But it demonstrates that lost brain tissue can be replaced with stem cells targeted at sites of damage.
Stem cells are immature cells with the ability to take on any of a number of specialist roles.
In previous animal experiments, stem cells implanted into the brain have tended to migrate to surrounding healthy tissue rather than fill up the hole left by a stroke.
Scientists from King's College London and the University of Nottingham overcame the problem by loading the cells onto biodegradable particles.
These were then injected through a fine needle to the precise site of damage, located using a magnetic resonance imaging (MRI) scanner.
Once implanted, the particles disappeared leaving gaps for the growth of new tissue and nourishing blood vessels.
The cells, derived from stem cells taken from mouse embryos, had already progressed some of the way to becoming neurons.
They were attached to particles made from a biodegradable plastic-like polymer called PLGA.
Dr Mike Modo, leading the King's College team from the university's Institute of Psychiatry, said: "The stem cell-loaded PLGA particles can be injected through a very fine needle and then adopt the precise shape of the cavity. In this process the cells fill the cavity and can make connections with other cells, which helps to establish the tissue.
"Over a few days we can see cells migrating along the scaffold particles and forming a primitive brain tissue that interacts with the host brain. Gradually the particles biodegrade leaving more gaps and conduits for tissue, fibres and blood vessels to move into."
Colleague Kevin Shakesheff, Professor of Advanced Drug Delivery and Tissue Engineering at the University of Nottingham, said: "This was a great collaborative project with the Kings College team and hopefully this technology will be taken to the clinical setting soon. Repairing damaged brain tissue is one of the ultimate challenges in medicine and science. It is great that we are now one step closer to achieving that goal."
The next stage will be to apply a "growth factor" chemical called VEGF with the particles to encourage the creation of new blood vessels.
The research, funded by the Biotechnology and Biological Sciences Research Council (BBSRC), is reported in the journal Biomaterials.
Strokes occur when part of the brain dies off because of a blocked or burst blood vessel.
An estimated 150,000 strokes occur in the UK each year, 67,000 of which are fatal.
Strokes cause more disability than any other chronic condition. Around 300,000 people in the UK are moderately or severely disabled because of a stroke.
Joe Korner, from the Stroke Association charity, said: "This research is another step towards using stem cell therapy in treating and reversing the brain damage caused by stroke. It is exciting because researchers have shown they are able to overcome some of the many challenges in translating the potential of using stem cells into reality.
"The potential to reverse the disabling effects of stroke seems to have been proved. However the development of stem cell therapy for stroke survivors is still in the early stages and much more research will be needed before it can be tested in humans or used in practice.
"Every five minutes someone in the UK has a stroke and it is vital that we do all we can to help those affected by stroke."
Professor Douglas Kell, chief executive of the BBSRC, said: "Stroke is a leading cause of disability in industrialised countries. It is reassuring to know that the technology for treating stroke by repairing brain damage is getting ever closer to translation into the clinic. This crucial groundwork by Dr Modo and his colleagues will surely be a solid foundation of basic research for much better treatments in the future."
Anthony Hollander, Professor of Rheumatology and Tissue Engineering at the University of Bristol, said: "We are only just beginning to understand how to use tissue engineering to cure diseases. This study shows the exciting possibility of using a biomaterial to deliver stem cells to a very specific location in the brain. It is too early to say if it will be clinically effective in patients but the more we explore these possibilities the more likely it is that we will develop successful therapies."
The Independent
Mon, 09 Mar 2009
Disabling strokes could one day be treated by replacing damaged brain tissue with stem cells, scientists have shown.
Researchers used a new technique to insert therapeutic stem cells into the brains of rats with pinpoint accuracy.
Once implanted the cells began to form new brain tissue and nerve connections.
The work is at an early stage and does not yet prove that stroke symptoms such as paralysis can be reversed.
But it demonstrates that lost brain tissue can be replaced with stem cells targeted at sites of damage.
Stem cells are immature cells with the ability to take on any of a number of specialist roles.
In previous animal experiments, stem cells implanted into the brain have tended to migrate to surrounding healthy tissue rather than fill up the hole left by a stroke.
Scientists from King's College London and the University of Nottingham overcame the problem by loading the cells onto biodegradable particles.
These were then injected through a fine needle to the precise site of damage, located using a magnetic resonance imaging (MRI) scanner.
Once implanted, the particles disappeared leaving gaps for the growth of new tissue and nourishing blood vessels.
The cells, derived from stem cells taken from mouse embryos, had already progressed some of the way to becoming neurons.
They were attached to particles made from a biodegradable plastic-like polymer called PLGA.
Dr Mike Modo, leading the King's College team from the university's Institute of Psychiatry, said: "The stem cell-loaded PLGA particles can be injected through a very fine needle and then adopt the precise shape of the cavity. In this process the cells fill the cavity and can make connections with other cells, which helps to establish the tissue.
"Over a few days we can see cells migrating along the scaffold particles and forming a primitive brain tissue that interacts with the host brain. Gradually the particles biodegrade leaving more gaps and conduits for tissue, fibres and blood vessels to move into."
Colleague Kevin Shakesheff, Professor of Advanced Drug Delivery and Tissue Engineering at the University of Nottingham, said: "This was a great collaborative project with the Kings College team and hopefully this technology will be taken to the clinical setting soon. Repairing damaged brain tissue is one of the ultimate challenges in medicine and science. It is great that we are now one step closer to achieving that goal."
The next stage will be to apply a "growth factor" chemical called VEGF with the particles to encourage the creation of new blood vessels.
The research, funded by the Biotechnology and Biological Sciences Research Council (BBSRC), is reported in the journal Biomaterials.
Strokes occur when part of the brain dies off because of a blocked or burst blood vessel.
An estimated 150,000 strokes occur in the UK each year, 67,000 of which are fatal.
Strokes cause more disability than any other chronic condition. Around 300,000 people in the UK are moderately or severely disabled because of a stroke.
Joe Korner, from the Stroke Association charity, said: "This research is another step towards using stem cell therapy in treating and reversing the brain damage caused by stroke. It is exciting because researchers have shown they are able to overcome some of the many challenges in translating the potential of using stem cells into reality.
"The potential to reverse the disabling effects of stroke seems to have been proved. However the development of stem cell therapy for stroke survivors is still in the early stages and much more research will be needed before it can be tested in humans or used in practice.
"Every five minutes someone in the UK has a stroke and it is vital that we do all we can to help those affected by stroke."
Professor Douglas Kell, chief executive of the BBSRC, said: "Stroke is a leading cause of disability in industrialised countries. It is reassuring to know that the technology for treating stroke by repairing brain damage is getting ever closer to translation into the clinic. This crucial groundwork by Dr Modo and his colleagues will surely be a solid foundation of basic research for much better treatments in the future."
Anthony Hollander, Professor of Rheumatology and Tissue Engineering at the University of Bristol, said: "We are only just beginning to understand how to use tissue engineering to cure diseases. This study shows the exciting possibility of using a biomaterial to deliver stem cells to a very specific location in the brain. It is too early to say if it will be clinically effective in patients but the more we explore these possibilities the more likely it is that we will develop successful therapies."
mardi 3 mars 2009
Two distinct molecular pathways can make regulatory immune cells
Finding a way to bypass the molecular events involved in autoimmunity - where the body's immune system mounts a self-directed attack - could lead to new treatments for autoimmune disorders and chronic infections. A study published in this week's issue of PLoS Biology describes genetic evidence that two distinct molecular pathways control the formation of regulatory T cells (Treg), a cell type vitally important in limiting undesirable immune responses.
Treg cells are like the peace-keepers of the immune defence system - they limit the actions of effector T cells, the foot-soldiers of the body. If the body lacks sufficient numbers of Treg cells, it loses the ability to tone down immune responses once invading pathogens are cleared. In addition, the body is unable to suppress T cell responses that recognize and target the body itself. The latter can lead to autoimmunity, which can destroy vital tissues and organs.
Under normal healthy conditions, the majority of Treg cells are derived from an organ called the thymus. New work from researchers at Cincinnati Children's Hospital Medical Center and The Scripps Research Institute in California, shows that if a gene called Carma1 isn't expressed normally, Treg development is impaired in the thymus. Mutations in Carma1 can result in a failure of the thymus to produce Treg cells, said senior investigator Kasper Hoebe, Ph.D., a researcher at Cincinnati.
But the study also points to a second molecular pathway - occurring in the peripheral lymphoid system - that is known to result in development of Treg cells. This means if the process in the thymus breaks down, as in the case with Carma1 mutations, Treg cells created in the peripheral lymphoid system can compensate.
"We show that the two pathways for Treg development are molecularly distinct, and Treg can arise quite well in the peripheral lymphoid system, via mechanisms that are independent of the thymic process," Dr. Hoebe said. "This is important because it shows the flexibility of the immune system to regulate T cell responses. If we understand the molecular requirements of these pathways we can potentially use these as targets for therapeutic intervention - which is the eventual goal."
Possible therapies may include the ability to repress the self-destructive immune response in autoimmune disease by increasing Treg development, or achieving the opposite effect to treat chronic infectious diseases - inhibiting Treg development and promoting activation of destructive T cells.
More information: Barnes MJ, Krebs P, Harris N, Eidenschenk C, Gonzalez-Quintial R, et al. (2009) Commitment to the regulatory T cell lineage requires CARMA1 in the thymus but not in the periphery. PLoS Biol 7(3): e1000051. doi:10.1371/journal.pbio.1000051, http://biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pbio.1000051
Source: Public Library of Science
Treg cells are like the peace-keepers of the immune defence system - they limit the actions of effector T cells, the foot-soldiers of the body. If the body lacks sufficient numbers of Treg cells, it loses the ability to tone down immune responses once invading pathogens are cleared. In addition, the body is unable to suppress T cell responses that recognize and target the body itself. The latter can lead to autoimmunity, which can destroy vital tissues and organs.
Under normal healthy conditions, the majority of Treg cells are derived from an organ called the thymus. New work from researchers at Cincinnati Children's Hospital Medical Center and The Scripps Research Institute in California, shows that if a gene called Carma1 isn't expressed normally, Treg development is impaired in the thymus. Mutations in Carma1 can result in a failure of the thymus to produce Treg cells, said senior investigator Kasper Hoebe, Ph.D., a researcher at Cincinnati.
But the study also points to a second molecular pathway - occurring in the peripheral lymphoid system - that is known to result in development of Treg cells. This means if the process in the thymus breaks down, as in the case with Carma1 mutations, Treg cells created in the peripheral lymphoid system can compensate.
"We show that the two pathways for Treg development are molecularly distinct, and Treg can arise quite well in the peripheral lymphoid system, via mechanisms that are independent of the thymic process," Dr. Hoebe said. "This is important because it shows the flexibility of the immune system to regulate T cell responses. If we understand the molecular requirements of these pathways we can potentially use these as targets for therapeutic intervention - which is the eventual goal."
Possible therapies may include the ability to repress the self-destructive immune response in autoimmune disease by increasing Treg development, or achieving the opposite effect to treat chronic infectious diseases - inhibiting Treg development and promoting activation of destructive T cells.
More information: Barnes MJ, Krebs P, Harris N, Eidenschenk C, Gonzalez-Quintial R, et al. (2009) Commitment to the regulatory T cell lineage requires CARMA1 in the thymus but not in the periphery. PLoS Biol 7(3): e1000051. doi:10.1371/journal.pbio.1000051, http://biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pbio.1000051
Source: Public Library of Science
samedi 28 février 2009
Un médicament améliore la marche de patients atteints de sclérose en plaques
PARIS (AFP) — Un médicament améliore la marche chez des malades atteints de sclérose en plaques et semble bien toléré, selon les résultats d'un essai clinique sur 300 personnes publiés vendredi dans la revue médicale The Lancet.
L'essai clinique de phase III (dernière étape avant la demande de mise sur le marché) a été conduit par Andrew Goodman (université de Rochester, New York) et ses collègues dans 33 centres de lutte contre la sclérose en plaques (SEP) aux Etats-Unis et au Canada.
301 personnes atteintes de SEP, âgées entre 18 et 70 ans, ont reçu pendant 14 semaines soit le médicament fampridine (10 mg deux fois par jour), soit un placebo.
La proportion des malades dont la vitesse de marche s'est améliorée était nettement supérieure dans le groupe traité avec la fampridine (35%) que dans le groupe témoin ayant reçu le placebo (8%), selon les résultats de cet essai.
La SEP, maladie neurologique particulièrement invalidante, provoque une dégradation de la gaine de myéline qui protège les fibres nerveuses (cerveau, moelle épinière et nerf optique), ce qui ralentit la vitesse de conduction de l'influx nerveux.
Cette maladie chronique, qui touche le plus souvent le jeune adulte, concerne quelque 80.000 personnes en France et 350.000 en Europe.
La fampridine n'agit pas sur le processus de démyélinisation mais contribue à améliorer la transmission de l'influx nerveux.
La société Acorda Therapeutics, qui a développé ce traitement, a déposé ce mois-ci une demande d'autorisation de mise sur le marché auprès de l'Agence américaine des médicaments (FDA).
Obtention de cellules souches neuronales
Des chercheurs de l'Université (Une université est un établissement d'enseignement supérieur dont l'objectif est la production du savoir (recherche),...) de Bonn ont réussi à obtenir des cellules souches neuronales à partir de cellules souches embryonnaires humaines.
Ces cellules présentent l'intérêt non seulement de pouvoir se conserver presque sans limite dans une culture (La définition que donne l'UNESCO de la culture est la suivante [1] :), mais également de servir de source presque inépuisable pour différents types de cellules nerveuses. Cette recherche (La recherche scientifique désigne en premier lieu l’ensemble des actions entreprises en vue de produire et de...) a aussi permis de démontrer que ces cellules nerveuses peuvent s'intégrer dans les circuits neuronaux du cerveau.
L'étude est publiée dans la prochaine édition de Proceedings of the National Academy of Sciences PNAS (doi: 10.1073/pnas.0808387106).
Pendant des années, la recherche sur les cellules souches a semblé divisée en deux mondes: les cellules sources embryonnaires au développement illimité d'une part, et les cellules souches somatiques qui peuvent être obtenues à partir de tissus d'adultes, mais ces dernières cellules étaient limitées dans leur potentiel de développement.
Les scientifiques de l'Université de Bonn ont rapproché ces deux mondes en créant des cellules souches du cerveau pouvant se multiplier et se conserver quasiment indéfiniment. C'est à partir de ces cellules que les chercheurs ont pu obtenir différentes cellules nerveuses dont des semblables à celles observées dans la maladie de Parkinson.
L'expérimentation sur des animaux a prouvé que ces cellules nerveuses obtenues artificiellement fonctionnaient bien. Les cellules transplantées sur des souris de laboratoire sont entrées en contact avec le cerveau du receveur pouvant émettre des signaux et en recevoir. Les chercheurs veulent utiliser cette source quasi inépuisable de cellules nerveuses humaines pour faire des études sur les maladies neuro-dégénératives.
Source: communiqué de presse de l'Université de Bonn
Illustration: Wikipédia
Ces cellules présentent l'intérêt non seulement de pouvoir se conserver presque sans limite dans une culture (La définition que donne l'UNESCO de la culture est la suivante [1] :), mais également de servir de source presque inépuisable pour différents types de cellules nerveuses. Cette recherche (La recherche scientifique désigne en premier lieu l’ensemble des actions entreprises en vue de produire et de...) a aussi permis de démontrer que ces cellules nerveuses peuvent s'intégrer dans les circuits neuronaux du cerveau.
L'étude est publiée dans la prochaine édition de Proceedings of the National Academy of Sciences PNAS (doi: 10.1073/pnas.0808387106).
Pendant des années, la recherche sur les cellules souches a semblé divisée en deux mondes: les cellules sources embryonnaires au développement illimité d'une part, et les cellules souches somatiques qui peuvent être obtenues à partir de tissus d'adultes, mais ces dernières cellules étaient limitées dans leur potentiel de développement.
Les scientifiques de l'Université de Bonn ont rapproché ces deux mondes en créant des cellules souches du cerveau pouvant se multiplier et se conserver quasiment indéfiniment. C'est à partir de ces cellules que les chercheurs ont pu obtenir différentes cellules nerveuses dont des semblables à celles observées dans la maladie de Parkinson.
L'expérimentation sur des animaux a prouvé que ces cellules nerveuses obtenues artificiellement fonctionnaient bien. Les cellules transplantées sur des souris de laboratoire sont entrées en contact avec le cerveau du receveur pouvant émettre des signaux et en recevoir. Les chercheurs veulent utiliser cette source quasi inépuisable de cellules nerveuses humaines pour faire des études sur les maladies neuro-dégénératives.
Source: communiqué de presse de l'Université de Bonn
Illustration: Wikipédia
jeudi 5 février 2009
Les cellules souches montrent leurs effets contre la sclérose en plaques
MaxiScience
2009-02-05
États-Unis - Un essai clinique mené par une équipe de l’université de Chicago montre que l'état des malades atteints de sclérose en plaques s'améliore après une autogreffe de cellules souches.
Vingt-et-un malades ont été transplantés avec leurs propres cellules souches extraites de leur moelle osseuse, après destruction de la moelle par immunosuppresseurs. Le système immunitaire est ainsi « remis à zéro ». Trois ans après cette transplantation, tous les malades n’ont pas connu d’aggravation de la maladie et dix-sept ont vu leur handicap réduire.
La sclérose en plaques est une affection neurologique grave qui pousse le système immunitaire à attaquer la myéline, couche protectrice des fibres nerveuses. Les inflammations sont constatées au niveau du cerveau, dans la moelle épinière et les nerfs. La sclérose en plaques évolue par poussées qui laissent des séquelles lourdes comme des troubles moteurs, des troubles de la coordination, des vertiges ou des problèmes de vue.
Aux différents stades de la maladie, des solutions chimiques existent. Cet essai a été réalisé sur des personnes trentenaires au premier stade de la maladie. Cette technique lourde de traitement ne sera pas applicable à tous les malades.
2009-02-05
États-Unis - Un essai clinique mené par une équipe de l’université de Chicago montre que l'état des malades atteints de sclérose en plaques s'améliore après une autogreffe de cellules souches.
Vingt-et-un malades ont été transplantés avec leurs propres cellules souches extraites de leur moelle osseuse, après destruction de la moelle par immunosuppresseurs. Le système immunitaire est ainsi « remis à zéro ». Trois ans après cette transplantation, tous les malades n’ont pas connu d’aggravation de la maladie et dix-sept ont vu leur handicap réduire.
La sclérose en plaques est une affection neurologique grave qui pousse le système immunitaire à attaquer la myéline, couche protectrice des fibres nerveuses. Les inflammations sont constatées au niveau du cerveau, dans la moelle épinière et les nerfs. La sclérose en plaques évolue par poussées qui laissent des séquelles lourdes comme des troubles moteurs, des troubles de la coordination, des vertiges ou des problèmes de vue.
Aux différents stades de la maladie, des solutions chimiques existent. Cet essai a été réalisé sur des personnes trentenaires au premier stade de la maladie. Cette technique lourde de traitement ne sera pas applicable à tous les malades.
La vitamine D pourrait prévenir la sclérose en plaques
PsychoMédia
05 février 2009
Une interaction directe entre la vitamine D et une variation génétique associée à la sclérose en plaques (SEP) modifie le risque de développer la maladie selon une récente étude publiée dans PLoS Genetics. L'étude suggère qu'une carence en vitamine D pendant la grossesse et durant les premières années pourrait augmenter le risque de développer la SEP plus tard dans la vie, considèrent les chercheurs.
La SEP est l'affection neurologique la plus fréquente chez les jeunes adules. Des facteurs génétiques et environnementaux sont à l'origine de la maladie.
Des études précédentes avaient montré que les populations des pays de l'Europe du Nord ont un risque plus élevé de SEP s'ils habitent dans des régions moins ensoleillées. Ce qui suggère un lien direct entre une carence en vitamine D, qui est produite par l'organisme en réponse à l'action de la lumière du soleil sur la peau, et un risque accru de SEP.
Le facteur génétique qui est de loin le plus important est la variation DRB1*1501, située sur le chromosome 6, et les séquences ADN adjacentes.
Des chercheurs de l'Université d'Oxford et de l'Université Columbia ont montré que des protéines activées par la vitamine D se lient à une séquence particulière de l'ADN qui se situe près de la variation DRB1*1501 et activent le gène.
"Chez les personnes qui portent la variation DRB1 associée à la sclérose en plaques, il semble que la vitamine D puisse joue un rôle critique", dit Dr Julian Knight, coauteur. "Si trop peu de vitamine est disponible, il est possible que le gène ne puisse pas fonctionner correctement". Ce gène agit sur le système immunitaire (rappelons que la SEP est une maladie auto-immune).
Cette étude suggère que de prendre des compléments de vitamine D durant la grossesse et durant les premières années pourrait réduire le risque de développer la SEP plus tard dans la vie", selon Dr Sreeram Ramagopalan qui a dirigé la recherche. (Il est difficile de combler les besoins en vitamine D par l'alimentation).
Psychomédia avec source:
Science Daily
05 février 2009
Une interaction directe entre la vitamine D et une variation génétique associée à la sclérose en plaques (SEP) modifie le risque de développer la maladie selon une récente étude publiée dans PLoS Genetics. L'étude suggère qu'une carence en vitamine D pendant la grossesse et durant les premières années pourrait augmenter le risque de développer la SEP plus tard dans la vie, considèrent les chercheurs.
La SEP est l'affection neurologique la plus fréquente chez les jeunes adules. Des facteurs génétiques et environnementaux sont à l'origine de la maladie.
Des études précédentes avaient montré que les populations des pays de l'Europe du Nord ont un risque plus élevé de SEP s'ils habitent dans des régions moins ensoleillées. Ce qui suggère un lien direct entre une carence en vitamine D, qui est produite par l'organisme en réponse à l'action de la lumière du soleil sur la peau, et un risque accru de SEP.
Le facteur génétique qui est de loin le plus important est la variation DRB1*1501, située sur le chromosome 6, et les séquences ADN adjacentes.
Des chercheurs de l'Université d'Oxford et de l'Université Columbia ont montré que des protéines activées par la vitamine D se lient à une séquence particulière de l'ADN qui se situe près de la variation DRB1*1501 et activent le gène.
"Chez les personnes qui portent la variation DRB1 associée à la sclérose en plaques, il semble que la vitamine D puisse joue un rôle critique", dit Dr Julian Knight, coauteur. "Si trop peu de vitamine est disponible, il est possible que le gène ne puisse pas fonctionner correctement". Ce gène agit sur le système immunitaire (rappelons que la SEP est une maladie auto-immune).
Cette étude suggère que de prendre des compléments de vitamine D durant la grossesse et durant les premières années pourrait réduire le risque de développer la SEP plus tard dans la vie", selon Dr Sreeram Ramagopalan qui a dirigé la recherche. (Il est difficile de combler les besoins en vitamine D par l'alimentation).
Psychomédia avec source:
Science Daily
Vitamin D is ray of sunshine for multiple sclerosis patients
Melanie Reid and Oliver Gillie
Times Online
Thu, 05 Feb 2009
Multiple sclerosis could be prevented through daily vitamin D supplements, scientists told The Times last night.
The first causal link has been established between the "sunshine vitamin" and a gene that increases the risk of MS, raising the possibility that the debilitating auto-immune disease could be eradicated.
George Ebers, Professor of Clinical Neurology at the University of Oxford, claimed that there was hard evidence directly relating both genes and the environment to the origins of MS.
His work suggests that vitamin D deficiency during pregnancy and childhood may increase the risk of a child developing the diease.
He has also established the possibility that genetic vulnerability to MS, apparently initiated by lack of vitamin D, may be passed through families.
These risks might plausibly be reduced by giving vitamin D supplements to pregnant woman and young children.
"I think it offers the potential for treatment which might prevent MS in the future," Professor Ebers said.
"Our research has married two key pieces of the puzzle. The interaction of vitamin D with the gene is very specific and it seems most unlikely to be a coincidence of any kind."
Warnings over sun exposure could now also be called into question - sunlight allows the body to produce the vitamin.
Professor Ebers said: "Serious questions now arise over the wisdom of current advice to limit sun exposure and avoid sunbathing. We also need to give better advice and help to the public on vitamin D supplements, particularly pregnant and nursing mothers."
The news has momentous implications for Scotland and other northern countries, where the incidence of multiple sclerosis is the highest in the world. It will give added urgency to recent moves by Scotland's Chief Medical Officer to consider recommending vitamin D supplements.
Deficiency in vitamin D, caused by lack of exposure to sunshine, has been increasingly linked to the cloudier climate in Scotland and other northern latitudes. The deficiency is twice as common among the Scots as it is amongst the English - and Orkney and Shetland have among the highest rates.
Studies have also shown that fewer people with MS are born in November and more in May, implicating a lack of sunshine during pregnancy.
The breakthrough comes after a groundswell of expert belief in the importance of vitamin D. Last November, at a conference organised by the Scottish Government, international experts urged vitamin D supplements for Scots to be tested "sooner rather than later" to find whether they could improve the nation's health.
Researchers for the World Health Organisation said there should be large, randomised trials as there was strong evidence that increased daily intake of vitamin D could significantly improve health.
The seminar followed evidence, revealed in The Times, that Scotland's poor health record has close links to vitamin D deficiency. Last September this newspaper reported evidence from scientists in Canada that children with early symptoms of multiple sclerosis have low levels of vitamin D.
Until now there has been no scientific proof of the links. However, Professor Ebers and his team have shown that vitamin D affects a particular genetic variant, identified as the one that increases the risk of developing MS threefold.
They suggest that a shortage of the vitamin alters this variant, thus preventing the immune system from functioning normally.
Professor Ebers said: "Whether it's at the core of MS is going to take some further work, but it does look like a reasonably good chance."
Last October Professor Ebers, in an article in The Times, backed the idea of distributing vitamin D supplements in Scotland to guard against conditions that may be linked to a deficiency, including MS.
"It is plausible that some 200 cases a year of MS might be prevented in Scotland alone by giving vitamin D to mothers and children," he wrote.
"Over a trial duration of 25 years, 5,000 cases of this disease might be otherwise prevented.
"The economic impact of each person with MS is at least an extra million pounds during a lifetime.
"Over 25 years £5 billion is at issue in this disease without factoring in the human cost, the increasing rate of MS or inflation. A large-scale programme providing vitamin D could provide scientific evidence."
Disease of the North: MS rates per 100,000 of the population
Canada 240
Scotland 150 - 200
Norway 110
England and Wales 90 - 110
Australia 78
Spain 59
Brazil 18
Sources: Atlas of Multiple Sclerosis
Times Online
Thu, 05 Feb 2009
Multiple sclerosis could be prevented through daily vitamin D supplements, scientists told The Times last night.
The first causal link has been established between the "sunshine vitamin" and a gene that increases the risk of MS, raising the possibility that the debilitating auto-immune disease could be eradicated.
George Ebers, Professor of Clinical Neurology at the University of Oxford, claimed that there was hard evidence directly relating both genes and the environment to the origins of MS.
His work suggests that vitamin D deficiency during pregnancy and childhood may increase the risk of a child developing the diease.
He has also established the possibility that genetic vulnerability to MS, apparently initiated by lack of vitamin D, may be passed through families.
These risks might plausibly be reduced by giving vitamin D supplements to pregnant woman and young children.
"I think it offers the potential for treatment which might prevent MS in the future," Professor Ebers said.
"Our research has married two key pieces of the puzzle. The interaction of vitamin D with the gene is very specific and it seems most unlikely to be a coincidence of any kind."
Warnings over sun exposure could now also be called into question - sunlight allows the body to produce the vitamin.
Professor Ebers said: "Serious questions now arise over the wisdom of current advice to limit sun exposure and avoid sunbathing. We also need to give better advice and help to the public on vitamin D supplements, particularly pregnant and nursing mothers."
The news has momentous implications for Scotland and other northern countries, where the incidence of multiple sclerosis is the highest in the world. It will give added urgency to recent moves by Scotland's Chief Medical Officer to consider recommending vitamin D supplements.
Deficiency in vitamin D, caused by lack of exposure to sunshine, has been increasingly linked to the cloudier climate in Scotland and other northern latitudes. The deficiency is twice as common among the Scots as it is amongst the English - and Orkney and Shetland have among the highest rates.
Studies have also shown that fewer people with MS are born in November and more in May, implicating a lack of sunshine during pregnancy.
The breakthrough comes after a groundswell of expert belief in the importance of vitamin D. Last November, at a conference organised by the Scottish Government, international experts urged vitamin D supplements for Scots to be tested "sooner rather than later" to find whether they could improve the nation's health.
Researchers for the World Health Organisation said there should be large, randomised trials as there was strong evidence that increased daily intake of vitamin D could significantly improve health.
The seminar followed evidence, revealed in The Times, that Scotland's poor health record has close links to vitamin D deficiency. Last September this newspaper reported evidence from scientists in Canada that children with early symptoms of multiple sclerosis have low levels of vitamin D.
Until now there has been no scientific proof of the links. However, Professor Ebers and his team have shown that vitamin D affects a particular genetic variant, identified as the one that increases the risk of developing MS threefold.
They suggest that a shortage of the vitamin alters this variant, thus preventing the immune system from functioning normally.
Professor Ebers said: "Whether it's at the core of MS is going to take some further work, but it does look like a reasonably good chance."
Last October Professor Ebers, in an article in The Times, backed the idea of distributing vitamin D supplements in Scotland to guard against conditions that may be linked to a deficiency, including MS.
"It is plausible that some 200 cases a year of MS might be prevented in Scotland alone by giving vitamin D to mothers and children," he wrote.
"Over a trial duration of 25 years, 5,000 cases of this disease might be otherwise prevented.
"The economic impact of each person with MS is at least an extra million pounds during a lifetime.
"Over 25 years £5 billion is at issue in this disease without factoring in the human cost, the increasing rate of MS or inflation. A large-scale programme providing vitamin D could provide scientific evidence."
Disease of the North: MS rates per 100,000 of the population
Canada 240
Scotland 150 - 200
Norway 110
England and Wales 90 - 110
Australia 78
Spain 59
Brazil 18
Sources: Atlas of Multiple Sclerosis
lundi 2 février 2009
Autologous non-myeloablative haemopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: a phase I/II study
The Lancet Neurology, Early Online Publication, 30 January 2009
Background
Autologous non-myeloablative haemopoietic stem cell transplantation is a method to deliver intense immune suppression. We evaluated the safety and clinical outcome of autologous non-myeloablative haemopoietic stem cell transplantation in patients with relapsing-remitting multiple sclerosis (MS) who had not responded to treatment with interferon beta.
Methods
Eligible patients had relapsing-remitting MS, attended Northwestern Memorial Hospital, and despite treatment with interferon beta had had two corticosteroid-treated relapses within the previous 12 months, or one relapse and gadolinium-enhancing lesions seen on MRI and separate from the relapse. Peripheral blood haemopoietic stem cells were mobilised with 2 g per m2 cyclophosphamide and 10 μg per kg per day filgrastim. The conditioning regimen for the haemopoietic stem cells was 200 mg per kg cyclophosphamide and either 20 mg alemtuzumab or 6 mg per kg rabbit antithymocyte globulin. Primary outcomes were progression-free survival and reversal of neurological disability at 3 years post-transplantation. We also sought to investigate the safety and tolerability of autologous non-myeloablative haemopoietic stem cell transplantation.
Findings
Between January, 2003, and February, 2005, 21 patients were treated. Engraftment of white blood cells and platelets was on median day 9 (range day 8—11) and patients were discharged from hospital on mean day 11 (range day 8—13). One patient had diarrhoea due to Clostridium difficile and two patients had dermatomal zoster. Two of the 17 patients receiving alemtuzumab developed late immune thrombocytopenic purpura that remitted with standard therapy. 17 of 21 patients (81%) improved by at least 1 point on the Kurtzke expanded disability status scale (EDSS), and five patients (24%) relapsed but achieved remission after further immunosuppression. After a mean of 37 months (range 24—48 months), all patients were free from progression (no deterioration in EDSS score), and 16 were free of relapses. Significant improvements were noted in neurological disability, as determined by EDSS score (p<0·0001), neurological rating scale score (p=0·0001), paced auditory serial addition test (p=0·014), 25-foot walk (p<0·0001), and quality of life, as measured with the short form-36 (SF-36) questionnaire (p<0·0001).
Interpretation
Non-myeloablative autologous haemopoietic stem cell transplantation in patients with relapsing-remitting MS reverses neurological deficits, but these results need to be confirmed in a randomised trial.
Funding
Division of Immunotherapy, Northwestern University.
Background
Autologous non-myeloablative haemopoietic stem cell transplantation is a method to deliver intense immune suppression. We evaluated the safety and clinical outcome of autologous non-myeloablative haemopoietic stem cell transplantation in patients with relapsing-remitting multiple sclerosis (MS) who had not responded to treatment with interferon beta.
Methods
Eligible patients had relapsing-remitting MS, attended Northwestern Memorial Hospital, and despite treatment with interferon beta had had two corticosteroid-treated relapses within the previous 12 months, or one relapse and gadolinium-enhancing lesions seen on MRI and separate from the relapse. Peripheral blood haemopoietic stem cells were mobilised with 2 g per m2 cyclophosphamide and 10 μg per kg per day filgrastim. The conditioning regimen for the haemopoietic stem cells was 200 mg per kg cyclophosphamide and either 20 mg alemtuzumab or 6 mg per kg rabbit antithymocyte globulin. Primary outcomes were progression-free survival and reversal of neurological disability at 3 years post-transplantation. We also sought to investigate the safety and tolerability of autologous non-myeloablative haemopoietic stem cell transplantation.
Findings
Between January, 2003, and February, 2005, 21 patients were treated. Engraftment of white blood cells and platelets was on median day 9 (range day 8—11) and patients were discharged from hospital on mean day 11 (range day 8—13). One patient had diarrhoea due to Clostridium difficile and two patients had dermatomal zoster. Two of the 17 patients receiving alemtuzumab developed late immune thrombocytopenic purpura that remitted with standard therapy. 17 of 21 patients (81%) improved by at least 1 point on the Kurtzke expanded disability status scale (EDSS), and five patients (24%) relapsed but achieved remission after further immunosuppression. After a mean of 37 months (range 24—48 months), all patients were free from progression (no deterioration in EDSS score), and 16 were free of relapses. Significant improvements were noted in neurological disability, as determined by EDSS score (p<0·0001), neurological rating scale score (p=0·0001), paced auditory serial addition test (p=0·014), 25-foot walk (p<0·0001), and quality of life, as measured with the short form-36 (SF-36) questionnaire (p<0·0001).
Interpretation
Non-myeloablative autologous haemopoietic stem cell transplantation in patients with relapsing-remitting MS reverses neurological deficits, but these results need to be confirmed in a randomised trial.
Funding
Division of Immunotherapy, Northwestern University.
Cellules souches - Résultats encourageants contre la sclérose en plaque
Cécile Dumas
Sciences-et-Avenir.com
30/01/09
Un petit essai clinique, mené sur 21 personnes atteintes de sclérose en plaques, montre qu’une ‘auto-greffe’ de cellules souches issues de la moelle osseuse permet d'améliorer l’état des patients. Ces résultats encourageants devront être vérifiés sur une plus large cohorte et comparés à d’autres traitements pour être consolidés.
Environ 80.000 personnes en France souffrent de cette maladie dont les formes et l’évolution varient grandement d’un patient à l’autre. La sclérose en plaque est caractérisée par une destruction de la myéline, la couche protectrice qui entoure les fibres nerveuses et qui transporte l’influx nerveux. Troubles de la coordination, problèmes de vue, vertiges, problèmes moteurs sont quelques-uns des symptômes de la maladie.
Il s’agit d’une affection auto-immune, autrement dit d’une attaque du système immunitaire, via des lymphocytes devenus agressifs, qui s’en prennent à l’organisme lui-même (en l’occurrence à la myéline). C’est pourquoi des chercheurs essaient de ‘’reprogrammer’’ le système immunitaire en greffant des cellules souches hématopoïétiques, issues de la moelle osseuse, précurseurs des globules rouges et des globules blancs (dont font partie les lymphocytes).
L’équipe de Richard Burt, de Chicago (USA), a prélevé des cellules souches hématopoïétiques chez les patients. Ceux-ci ont ensuite subi un traitement destiné à détruire les lymphocytes qui attaquent leur myéline avant de recevoir une greffe autologue de cellules souches. Trois ans après, 17 patients sur 21 ont connu une amélioration de leur état (définie comme un point gagné sur l’échelle de Kurtzke utilisée pour décrire l’évolution de la maladie)*.
Ce n’est pas la première fois que cette technique est testée sur des personnes mais les précédents essais n’avaient pas obtenus de résultats concluants. La différence tient à l’âge des patients et au stade de la maladie : il s’agit de trentenaires dont la sclérose évolue par poussées, suivies de périodes de rémissions. C’est généralement la première phase de la maladie (dite forme rémittente), suivie d’une phase progressive où les symptômes semblent irréversibles.
* Travaux publiés en ligne (édition anticipée) par The Lancet Neurology (en mars dans la revue papier).
Sciences-et-Avenir.com
30/01/09
Un petit essai clinique, mené sur 21 personnes atteintes de sclérose en plaques, montre qu’une ‘auto-greffe’ de cellules souches issues de la moelle osseuse permet d'améliorer l’état des patients. Ces résultats encourageants devront être vérifiés sur une plus large cohorte et comparés à d’autres traitements pour être consolidés.
Environ 80.000 personnes en France souffrent de cette maladie dont les formes et l’évolution varient grandement d’un patient à l’autre. La sclérose en plaque est caractérisée par une destruction de la myéline, la couche protectrice qui entoure les fibres nerveuses et qui transporte l’influx nerveux. Troubles de la coordination, problèmes de vue, vertiges, problèmes moteurs sont quelques-uns des symptômes de la maladie.
Il s’agit d’une affection auto-immune, autrement dit d’une attaque du système immunitaire, via des lymphocytes devenus agressifs, qui s’en prennent à l’organisme lui-même (en l’occurrence à la myéline). C’est pourquoi des chercheurs essaient de ‘’reprogrammer’’ le système immunitaire en greffant des cellules souches hématopoïétiques, issues de la moelle osseuse, précurseurs des globules rouges et des globules blancs (dont font partie les lymphocytes).
L’équipe de Richard Burt, de Chicago (USA), a prélevé des cellules souches hématopoïétiques chez les patients. Ceux-ci ont ensuite subi un traitement destiné à détruire les lymphocytes qui attaquent leur myéline avant de recevoir une greffe autologue de cellules souches. Trois ans après, 17 patients sur 21 ont connu une amélioration de leur état (définie comme un point gagné sur l’échelle de Kurtzke utilisée pour décrire l’évolution de la maladie)*.
Ce n’est pas la première fois que cette technique est testée sur des personnes mais les précédents essais n’avaient pas obtenus de résultats concluants. La différence tient à l’âge des patients et au stade de la maladie : il s’agit de trentenaires dont la sclérose évolue par poussées, suivies de périodes de rémissions. C’est généralement la première phase de la maladie (dite forme rémittente), suivie d’une phase progressive où les symptômes semblent irréversibles.
* Travaux publiés en ligne (édition anticipée) par The Lancet Neurology (en mars dans la revue papier).
Turning down gene expression promotes nerve cell maintenance
February 2nd, 2009
Anyone with a sweet tooth knows that too much of a good thing can lead to negative consequences. The same can be said about the signals that help maintain nerve cells, as demonstrated in a new study of myelin, a protein key to efficient neuronal transmission.
Normal nerve cells have a myelin sheath, which, much like the insulation on a cable, allows for rapid and efficient signal conduction. However, in several diseases - the most well-known being multiple sclerosis - demyelination processes cause the breakdown of this "insulation", and lead to deficits in perception, movement, cognition, etc. Thus, in order to help patients of demyelinating disease, researchers are studying the pathways that control myelin formation and maintenance.
A new study by University of California scientists examines the role of a structural protein, called lamin, in maintaining myelin. They found that, while lamin is necessary in the initial stages of myelin formation, too much lamin promotes myelin breakdown. Further investigation led the researchers to the discovery of a signal that fine-tunes lamin expression. This signal, a microRNA called miR-23, can turn down lamin gene expression, and thereby prevent demyelination due to lamin overexpression.
This new work reported in Disease Models & Mechanisms (DMM), adds another piece to the puzzle that is understanding myelin formation and maintenance. Additionally, the identification of miR-23 as a myelin regulator introduces a new potential drug target in developing treatments for demyelinating illness.
The report was written Shu-Ting Lin and Ying-Hui Fu at the Department of Neurology, University of California San Francisco. The report is published in the March/April issue of Disease Models & Mechanisms (DMM), a research journal published by The Company of Biologists, a non-profit based in Cambridge, UK.
Anyone with a sweet tooth knows that too much of a good thing can lead to negative consequences. The same can be said about the signals that help maintain nerve cells, as demonstrated in a new study of myelin, a protein key to efficient neuronal transmission.
Normal nerve cells have a myelin sheath, which, much like the insulation on a cable, allows for rapid and efficient signal conduction. However, in several diseases - the most well-known being multiple sclerosis - demyelination processes cause the breakdown of this "insulation", and lead to deficits in perception, movement, cognition, etc. Thus, in order to help patients of demyelinating disease, researchers are studying the pathways that control myelin formation and maintenance.
A new study by University of California scientists examines the role of a structural protein, called lamin, in maintaining myelin. They found that, while lamin is necessary in the initial stages of myelin formation, too much lamin promotes myelin breakdown. Further investigation led the researchers to the discovery of a signal that fine-tunes lamin expression. This signal, a microRNA called miR-23, can turn down lamin gene expression, and thereby prevent demyelination due to lamin overexpression.
This new work reported in Disease Models & Mechanisms (DMM), adds another piece to the puzzle that is understanding myelin formation and maintenance. Additionally, the identification of miR-23 as a myelin regulator introduces a new potential drug target in developing treatments for demyelinating illness.
The report was written Shu-Ting Lin and Ying-Hui Fu at the Department of Neurology, University of California San Francisco. The report is published in the March/April issue of Disease Models & Mechanisms (DMM), a research journal published by The Company of Biologists, a non-profit based in Cambridge, UK.
dimanche 18 janvier 2009
Eyes reveal health secrets of the brain
Duncan Graham-Rowe
New Scientist
Sun, 18 Jan 2009
The eyes may be the windows to the soul, but they also make pretty good peepholes into the brain. Thanks to an optical version of ultrasound, it is becoming possible to locate and monitor the growth of brain tumours, and to track neurodegenerative conditions like multiple sclerosis, Alzheimer's and Parkinson's disease - all by peering into the eye.The brain is connected to each eye by an optic nerve, so any degeneration of the brain caused by such diseases can also damage cells along the nerve and in the retina, says Helen Danesh-Meyer, an eye surgeon and neuro-ophthalmologist at the University of Auckland Medical School in New Zealand. Indeed, a loss of visual function is one of the first symptoms in many people with a neurodegenerative condition.
Although evidence of a link between degeneration of the optic nerve and diseases such as Alzheimer's has been around since the late 1980s, without instruments capable of measuring the retinal changes accurately it is only recently that this knowledge could be put to use, says Danesh-Meyer.
The accuracy of ophthalmological tools has greatly improved in the last few years. Developments include a type of laser-camera technique called Heidelberg retina tomography (HRT), and a laser device called GDx, both of which can be used to scan the shape and thickness of optical nerve fibres at the back of the eye.
Both tools are now widely used to manage glaucoma, but in 2006 Danesh-Meyer became one of the first researchers to use them to study neurodegenerative diseases by looking at the region of the retina where ganglion cells meet to form the optic nerve - a region known as the optic nerve disc (OND). In a trial involving 40 Alzheimer's patients and 50 healthy volunteers, she was able to show that people with Alzheimer's had a distinctive enlargement to a cup-shaped part of their OND and a progressive thinning of the retinal nerve fibres within the disc.
Following this discovery, researchers have been using even more accurate instruments to track degenerative changes in the OND to monitor the progression of diseases like Alzheimer's, Parkinson's and MS. But it has been the emergence of optical coherence tomography (OCT) that appears most promising: it became commercially available in 2006 and is fast becoming a standard tool for the management of glaucoma and diabetic retinopathy. When applied to the OND, it produces highly detailed two and three-dimensional images of the subsurface retinal tissue, says Denise Valenti at Boston University, who has been using OCT to study Parkinson's and Alzheimer's.
The technique works very much like ultrasound, but bounces light off the tissue instead of sound waves. One beam of light is fired at the tissue and another at a reference mirror. When the reflected beams have travelled an identical distance, interference will make their combined beam brighter than if the distances are different. So by reflecting one beam off of different layers of tissue, and moving the reference mirror until the combined reflected beam is brightest, the technique can measure the depths of each section of tissue and build up a detailed image of its structure.
It has proved particularly useful in ophthalmology because the semi-transparent nature of retinal tissue makes it possible for OCT to penetrate to greater depths - up to several millimetres. When applied to the OND it can give information about both the shape and thickness of retinal nerve fibres, allowing even subtle changes to be tracked.
Such changes can be used to monitor the progression of diseases non-invasively and relatively cheaply. Unlike MRI, which is expensive and can require patients to remain still for an hour or more, OCT is increasingly available in clinics and can be carried out in a few minutes. "It's extremely inexpensive compared to other tests," says Valenti.
MRI : IRM
One possibility is to use OCT to monitor the effectiveness of treatments for neurodegenerative diseases, says Danesh-Meyer: "These drugs can have a lot of side effects, so if they are not having a benefit then you won't want to continue with them."
Laura Balcer, a neurologist at the University of Pennsylvania School of Medicine in Philadelphia, has been using OCT on patients taking part in MS drug trials to try to establish if the system can accurately gauge drug efficacy. Such an objective tool would allow symptoms to be picked up that might otherwise go unreported, she says. For example, OCT has already shown that even in people with MS whose eye function is normal, there are marked differences in OND shape and fibre thickness compared with healthy people. "MS researchers are very excited about OCT," she says.
The technology is also proving its value as a tool for monitoring brain tumours, which can affect vision by pressing on the optic nerve. Such pressure will cause damage to different parts of the OND, depending on where in the brain the tumour is located, says Danesh-Meyer. What's more, the extent of the thinning of the nerve-disc fibre can also reveal whether vision will be restored upon removal of the tumour.
In the case of one patient who was 24 weeks pregnant following several IVF attempts, OCT monitoring allowed surgeons to hold off on removing her brain tumour until well into the third trimester, when the fetus had a better chance of survival. The usual treatment would have been to operate immediately to prevent permanent vision loss, but this would have risked inducing premature labour. By monitoring the compression on the optic nerve to ensure it did not reach the point at which permanent damage was inevitable, Danesh-Meyer was able to keep tabs on the tumour's growth and delay the surgery. As a result, the baby was born safely and the patient kept her vision.
The ultimate aim for many using OCT is to diagnose diseases before symptoms arise. The difficulty with this is that the thickness of retinal nerve fibres can vary from person to person, says Danesh-Meyer, so there is not always a clear baseline from which to compare patient scans.
Eventually though, the low cost and simplicity of the technology may make it feasible for people to be given an OCT scan of each eye at a young age, to give doctors a record of their healthy retinal nerve, says Danesh-Meyer. With regular screening, some neurological conditions could be spotted incredibly early. "We're really just at the cusp of knowing where this is all going."
mercredi 7 janvier 2009
Extreme Mercury Toxicity Sidelines Actor Jeremy Piven
Chicago actor Jeremy Piven has unexpectedly left the cast of the Broadway revival of "Speed-the-Plow" because of a mercury count that his doctor said was the highest level he'd ever seen.
Piven, 43, wanted to continue but he was advised to stop. Dr. Carlon Colker, who had been treating Piven, said Piven was suffering from "extreme mercury toxicity" and that "a test revealed that Jeremy had ... six times a healthy amount of mercury in his system." Piven has long been a sushi eater, often twice a day, which may be the ultimate cause of the problem.
A major symptom of mercury poisoning is extreme fatigue. Piven was also experiencing neuro-muscular dysfunction, which resulted in his having trouble lifting his arms and legs.
Piven has won Emmy Awards for his role as foul-mouthed Hollywood agent Ari Gold in the HBO series Entourage. He had been performing to critical praise in "Speed-the-Plow" since October.
http://articles.mercola.com/sites/articles/archive/2009/01/06/extreme-mercury-toxicity-sidelines-actor-jeremy-piven.aspx
Piven, 43, wanted to continue but he was advised to stop. Dr. Carlon Colker, who had been treating Piven, said Piven was suffering from "extreme mercury toxicity" and that "a test revealed that Jeremy had ... six times a healthy amount of mercury in his system." Piven has long been a sushi eater, often twice a day, which may be the ultimate cause of the problem.
A major symptom of mercury poisoning is extreme fatigue. Piven was also experiencing neuro-muscular dysfunction, which resulted in his having trouble lifting his arms and legs.
Piven has won Emmy Awards for his role as foul-mouthed Hollywood agent Ari Gold in the HBO series Entourage. He had been performing to critical praise in "Speed-the-Plow" since October.
http://articles.mercola.com/sites/articles/archive/2009/01/06/extreme-mercury-toxicity-sidelines-actor-jeremy-piven.aspx
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