| THE UNIVERSITY OF NEW SOUTH WALES |
Australian researchers have uncovered a potential new way to regulate the body’s natural immune response, offering hope of a simple and effective treatment for auto-immune diseases.
Auto-immune diseases result from an overactive immune response that causes the body to attack itself. The new approach involves increasing good regulating cells in the body, unlike most current research focusing on stopping “bad” or “effector” cells, says lead researcher Dr Suzanne Hodgkinson from UNSW’s Faculty of Medicine and Liverpool Hospital. The researchers induced the body’s T-cell front-line defences by injecting cell-signalling proteins called cytokines, particularly Interleukin-5 (II-5 cytokine). When T-regulatory cells are grown in a way that makes them specific to a particular protein, they develop receptors for the Il-5 cytokine. The Il-5 cytokine boost allows the body’s immune system to better regulate its response to disease without going into overdrive. The team cloned II-5 cytokine and injected it into rats with the neurological condition Guillain–Barré syndrome. These rats recovered much quicker and did not fall ill if treated as a precaution. The method has also shown promise in animals with multiple sclerosis, kidney disease, nephritis and trying to overcome organ transplantation rejection. “One of the nice things about this discovery is that it is one of the few treatments in the auto-immune world and in the transplantation world that works not by attacking the effector cells but by increasing the good regulating cells. So it works very differently from almost every other treatment we’ve got available,” Dr Hodgkinson says. The researchers say that il-5 injections could be more palatable than inoculation by parasitic worms – another approach in regulating auto-immune conditions. International research shows swallowing helminth parasites can regulate the immune system and boost T-cell production to combat illnesses such as celiac disease and multiple sclerosis. The absence of worms in guts in the developed world has been cited as a possible cause for the sharp rise in auto-immune diseases in Western nations. “The process we’ve developed may be the same process that the helminths kick off. When you get a helminths infestation, one of the changes in your immune response is an increase in cells called eosinophils and these cells make the cytokine Interleukin-5,” Dr Hodgkinson says. “In this new treatment, it’s a matter of injecting the interleukin-5 and the body does the rest. It’s both safe and effective and we think inducing the immune response by injection may be more attractive to people than swallowing parasitic worms.” The next step is to take the treatment to human trials, which could be underway within two to five years, says Dr Hodgkinson, whose paper outlining the study has been published in the journalBlood. The research was supported by grants from Bob and Jack Ingham, Liverpool Australia; Multiple Sclerosis Research Australia; the Australian National Health and Medical Research Council; the Juvenile Diabetes Research Foundation; Novatis; and funds from UNSW. Lead researcher was UNSW research fellow Dr Giang Tran. Dr Hodgkinson and co-author Professor Bruce Hall hold US patents related to the treatment.
Editor's Note: Original news release can be found here.
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Tuesday, June 5, 2012
New auto-immune treatment hope
Magnets to direct cancer drugs
| THE UNIVERSITY OF SYDNEY |
The new drug could greatly reduce or even eliminate the side effects of treatments such as chemotherapy, according to the researchers.
Image: klenger/iStockphoto
For more than three decades scientists have been investigating magnetic nanoparticles as a method of drug delivery. Now by combining three metals - iron, gold and platinum - pharmacists at the University of Sydney believe they have discovered a method for magnetically directing drugs through the body.
The discovery has been published online today in the international journal Inorganica Chimica Acta. Led by Dr Nial Wheate, a team of scientists from the Faculty of Pharmacy, along with collaborators in Scotland, have developed a new anticancer drug that has an iron oxide core as small as 5 nanometres in size (1/1000th the width of a human hair). "We coated this iron oxide core in a protective layer of gold before cisplatin, a platinum drug that revolutionised the treatment of testicular cancer, was attached to the gold coating using spaghetti-like strings of polymer." The important thing about this new drug, says Dr Wheate, is the ability of its iron core to move under the influence of a magnet; similar to the iron filing experiments many people have performed in science classes. "When we take regular medication it is difficult to manage where it goes. But this discovery means we can potentially direct exactly where in the human body a drug goes. We can move it to the desired cancer tumour site using powerful magnetic fields. Otherwise, a strong magnet could be implanted into a tumour, and draw the drug into the cancer cells that way." The technology was demonstrated when the team grew cancer cells in plates in the lab. When they placed a magnet under the plates, the drug affected and killed only those cells growing near the magnet, leaving the others unharmed, says Dr Wheate. "Many of the side-effects associated with chemotherapy occur because the drugs spread throughout the body, killing healthy organs as well as cancers. "Ultimately, this technology could greatly reduce or even eliminate the severe side-effects that people associate with chemotherapy such as hair loss, nausea, vomiting, low red blood cells and an increased risk of infection." This new drug technology could also be used to treat a range of cancers that have not been treatable with conventional platinum drugs, like prostate cancer. Platinum drugs are one of the most regularly used family of agents in chemotherapy and include cisplatin, carboplatin and oxaliplatin.
Editor's Note: Original news release can be found here.
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A different drummer: Neural rhythms drive physical movement
The 19th century mathematician Joseph Fourier showed that two rhythms could be summed to produce a third rhythm. Researchers at Stanford have shown that this principle is behind the brain activity that produces arm movements. Credit: Mark Churchland, Stanford School of Engineering
Unlike their visual cousins, the neurons that control movement are not a predictable bunch. Scientists working to decode how such neurons convey information to muscles have been stymied when trying to establish a one-to-one relationship between a neuron's behavior and external factors such as muscle activity or movement velocity.
In an article published online June 3rd by the journal Nature, a team of electrical engineers and neuroscientists working at Stanford University propose a new theory of the brain activity behind arm movements. Their theory is a significant departure from existing understanding and helps to explain, in relatively simple and elegant terms, some of the more perplexing aspects of the activity of neurons in motor cortex.
In their paper, electrical engineering Associate Professor Krishna Shenoy and post-doctoral researchers Mark Churchland, now a professor at Columbia, and John Cunningham of Cambridge University, now a professor at Washington University in Saint Louis, have shown that the brain activity controlling arm movement does not encode external spatial information—such as direction, distance and speed—but is instead rhythmic in nature.
Understanding the brain
Neuroscientists have long known that the neurons responsible for vision encode specific, external-world information—the parameters of sight. It had been theorized and widely suggested that motor cortex neurons function similarly, conveying specifics of movement such as direction, distance and speed, in the same way the visual cortex records color, intensity and form.
"Visual neurons encode things in the world. They are a map, a representation," said Churchland, who is first author of the paper. "It's not a leap to imagine that neurons in the motor cortex should behave like neurons in the visual cortex, relating in a faithful way to external parameters, but things aren't so concrete for movement."
Scientists have disagreed about which movement parameters are being represented by individual neurons. They could not look at a particular neuron firing in the motor cortex and determine with confidence what information it was encoding.
"Many experiments have sought such lawfulness and yet none have found it. Our findings indicate an alternative principle is at play," said co-first author Cunningham.
"Our main finding is that the motor cortex is a flexible pattern generator, and sends rhythmic signals down the spinal cord," said Churchland.
Engine of movement
To employ an automotive analogy, the motor cortex is not the steering wheel, odometer or speedometer representing real-world information. It is more like an engine, comprised of parts whose activities appear complicated in isolation, but which cooperate in a lawful way as a whole to generate motion.
"If you saw a piston or a spark plug by itself, would you be able to explain how it makes a car move?" asked Cunningham rhetorically. "Motor-cortex neurons are like that, too, understandable only in the context of the whole."
In a series of striking graphs, the Stanford team plotted the signals from individual neurons in the motor-cortex as monkeys completed a series of reaches. The reaching motions are shown by the starburst patterns at the top left of each graph. The neuronal patterns are then plotted atop one another for the entire series of reaches, clearly establishing the rhythmic nature of the brain activity. Credit: Mark Churchland, Stanford School of Engineering
The electrical signal that drives a given movement is therefore an amalgam – a summation – of the rhythms of all the motor neurons firing at a given moment.
"Under this new way of looking at things, the inscrutable becomes predictable," said Churchland. "Each neuron behaves like a player in a band. When the rhythms of all the players are summed over the whole band, a cascade of fluid and accurate motion results."
Dr. Daofen Chen, Program Director, Systems and Cognitive Neuroscience at the National Institute of Neurological Disorders and Stroke at the National Institutes of Health, said Shenoy and team are working at the cutting edge of the field. "In trying to find the basic response properties of the motor cortex, Dr. Shenoy and his colleagues are searching for the holy grail of neuroscience," said Dr. Chen. "His team has been consistent in tackling important but tough questions, often in thought-provoking ways and in ambitious proposals. NIH is proud to support this kind of pioneering and transformative research."
Precedents in nature
In the new model, a few relatively simple rhythms explain neural features that had confounded science earlier.
"Many of the most-baffling aspects of motor-cortex neurons seem natural and straightforward in light of this model," said Cunnigham.
The team studied non-rhythmic reaching movements, which made the presence of rhythmic neural activity a surprise even though, the team notes, rhythmic neural activity has a long precedence in nature. Such rhythms are present in the swimming motion of leeches and the gait of a walking monkey, for instance.
"The brain has had an evolutionary goal to drive movements that help us survive. The primary motor cortex is key to these functions. The patterns of activity it displays presumably derive from evolutionarily older rhythmic motions such as swimming and walking. Rhythm is a basic building block of movement," explained Churchland.
Reaching for the grail
To test their hypothesis, the engineers studied the brain activity of monkeys reaching to touch a target. According to the researchers, experiments show this 'underlying rhythm' strategy works very well to explain both brain and muscle activity. In their reaching studies, the pattern of shoulder-muscle behavior could always be described by the sum of two underlying rhythms.
"Say you're throwing a ball. Beneath it all is a pattern. Maybe your shoulder muscle contracts, relaxes slightly, contracts again, and then relaxes completely, all in short order," explained Churchland. "That activity may not be exactly rhythmic, but it can be created by adding together two or three other rhythms. Our data argue that this may be how the brain solves the problem of creating the pattern of movement."
"Finding these brain rhythms surprised us a bit, as the reaches themselves were not rhythmic. In fact, they were decidedly arrhythmic, and yet underlying it all were these unmistakable patterns," said Churchland.
"This research builds on a strong theoretical framework and adds to growing evidence that rhythmic activity is important for many fundamental brain functions," said Yuan Liu of the National Institute of Neurological Disorders and Stroke, NIH. "Further research in this area may help us devise more effective technology for controlling prosthetic limbs." Liu is the co-lead of the NIH-NSF Collaborative Research in Computational Neuroscience program.
"In this model, the seemingly complex system that is the motor cortex can now be at least partially understood in more straightforward terms. The motor cortex is an engine of movement that obeys lawful dynamics," said Shenoy.
Stanford post-doctoral fellow Matthew Kaufman, bioengineering PhD student and medical science training program student Paul Nuyujukian, electrical engineering graduate student Justin Foster, and electrical engineering consulting assistant professor and Palo Alto Medical Foundation neurosurgeon Stephen Ryu were also authors on this paper.
Provided by Stanford University
"A different drummer: Neural rhythms drive physical movement." June 3rd, 2012.http://medicalxpress.com/news/2012-06-drummer-neural-rhythms-physical-movement.html
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Robert Karl Stonjek
Robert Karl Stonjek
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