Posts tagged medicine
Articles and news from the latest research reports.
Brain Tumor Removal Through a Hole Smaller Than a Dime
More than two decades ago, Ryan Vincent had open brain surgery to remove a malignant brain tumor, resulting in a lengthy hospital stay and weeks of recovery at home. Recently, neurosurgeons at Houston Methodist Hospital removed a different lesion from Vincent’s brain through a tube inserted into a hole smaller than a dime and he went home the next day.
Gavin Britz, MBBCh, MPH, FAANS, chairman of neurosurgery at Houston Methodist Neurological Institute, used a minimally-invasive technique to remove a vascular lesion from deep within the 44-year-old patient’s brain, the first to use this technique in the region. Traditionally, vascular lesions or brain tumors that are located deep within the brain can cause damage just by surgical removal.
“With this new approach, we can navigate through millions of important brain fibers and tracts to access deep areas of the brain where these benign tumors or hemorrhages are located with minimal injury to normal brain,” said Britz. “Ryan’s surgery took less than an hour.”
Houston Methodist neurosurgeons Britz and David Baskin, M.D., director of the Kenneth R. Peak Brain & Pituitary Tumor Center, are using this “six-pillar approach” that encompasses the latest technology in minimally-invasive surgeries — mapping of the brain; navigating the brain like a GPS system; safely accessing the brain and tumor/lesion; using high-end optics for visualization; successfully removing the tumor without disrupting tissues around it; and directed therapy using tissue collected for evaluation that can then be used for personalized treatments.
The new surgical technique is used to remove cancerous and non-cancerous tumors, lesions and cysts deep inside the brain. This approach reduces risks of damage to speech, memory, muscle strength, balance, vision, coordination and other function areas of the brain.
(Source: newswise.com)
Stem cells linked to cognitive gain after brain injury in preclinical study
A stem cell therapy previously shown to reduce inflammation in the critical time window after traumatic brain injury also promotes lasting cognitive improvement, according to preclinical research led by Charles Cox, M.D., at The University of Texas Health Science Center at Houston (UTHealth) Medical School.
The research was published in today’s issue of STEM CELLS Translational Medicine.
Cellular damage in the brain after traumatic injury can cause severe, ongoing neurological impairment and inflammation. Few pharmaceutical options exist to treat the problem. About half of patients with severe head injuries need surgery to remove or repair ruptured blood vessels or bruised brain tissue.
A stem cell treatment known as multipotent adult progenitor cell (MAPC) therapy has been found to reduce inflammation in mice immediately after traumatic brain injury, but no one had been able to gauge its usefulness over time.
The research team led by Cox, the Children’s Fund, Inc. Distinguished Professor of Pediatric Surgery at the UTHealth Medical School, injected two groups of brain-injured mice with MAPCs two hours after the mice were injured and again 24 hours later. One group received a dose of 2 million cells per kilogram and the other a dose five times stronger.
After four months, the mice receiving the stronger dose not only continued to have less inflammation—they also made significant gains in cognitive function. A laboratory examination of the rodents’ brains confirmed that those receiving the higher dose of MAPCs had better brain function than those receiving the lower dose.
“Based on our data, we saw improved spatial learning, improved motor deficits and fewer active antibodies in the mice that were given the stronger concentration of MAPCs,” Cox said.
The study indicates that intravenous injection of MAPCs may in the future become a viable treatment for people with traumatic brain injury, he said.
(Source: uthouston.edu)
Important breakthrough in identifying the effect of epilepsy treatment
50 years after valproate was first discovered, research published today in the journal Neurobiology of Disease, reports how the drug works to block seizure progression.
Valproate (variously labelled worldwide as Epilim, Depacon, Depakene, Depakote, Orlept, Episenta, Orfiril, and Convulex) is one of the world’s most highly prescribed treatments for epilepsy. It was first discovered to be an effective treatment for epilepsy, by accident, in 1963 by a group of French scientists. In thousands of subsequent experiments, animals have been used to investigate how valproate blocks seizures, without success. Scientists from Royal Holloway and University College London have now identified how valproate blocks seizures in the brain, by using a simple amoeba.
“The discovery of how valproate blocks seizures, initially using the social amoeba Dictyostelium, and then replicated using accepted seizure models, highlights the successful use of non-animal testing in biomedical research,” said Professor Robin Williams from the School of Biological Sciences at Royal Holloway.
“Sodium valproate is one of the most effective antiepileptic drugs in many people with epilepsy, but its use has been limited by side-effects, in particular its effect in pregnant women on the unborn child,” said Professor Matthew Walker from the Institute of Neurology at University College London. “Understanding valproate’s mechanism of action is a first step to developing even more effective drugs that lack many of valproate’s side-effects.
“Our study also found that the decrease of a specific chemical in the brain at the start of the seizure causes even more seizure activity. This holds important implications for identifying underlying causes,” added Professor Williams.
(Source: rhul.ac.uk)
Incurable Brain Cancer Gene Is Silenced
Gene regulation technology increases survival rates in mice with glioblastoma
Glioblastoma multiforme (GBM), the brain cancer that killed Sen. Edward Kennedy and kills approximately 13,000 Americans a year, is aggressive and incurable. Now a Northwestern University research team is the first to demonstrate delivery of a drug that turns off a critical gene in this complex cancer, increasing survival rates significantly in animals with the deadly disease.
Image: Researchers combined gold nanoparticles (in yellow) with small interfering RNAs (in green) to knock down an oncogene that is overexpressed in glioblastoma.
The novel therapeutic, which is based on nanotechnology, is small and nimble enough to cross the blood-brain barrier and get to where it is needed — the brain tumor. Designed to target a specific cancer-causing gene in cells, the drug simply flips the switch of the troublesome oncogene to “off,” silencing the gene. This knocks out the proteins that keep cancer cells immortal.
In a study of mice, the nontoxic drug was delivered by intravenous injection. In animals with GBM, the survival rate increased nearly 20 percent, and tumor size was reduced three to four fold, as compared to the control group. The results are published today (Oct. 30) in Science Translational Medicine.
“This is a beautiful marriage of a new technology with the genes of a terrible disease,” said Chad A. Mirkin, a nanomedicine expert and a senior co-author of the study. “Using highly adaptable spherical nucleic acids, we specifically targeted a gene associated with GBM and turned it off in vivo. This proof-of-concept further establishes a broad platform for treating a wide range of diseases, from lung and colon cancers to rheumatoid arthritis and psoriasis.”
Mirkin is the George B. Rathmann Professor of Chemistry in the Weinberg College of Arts and Sciences and professor of medicine, chemical and biological engineering, biomedical engineering and materials science and engineering.
Glioblastoma expert Alexander H. Stegh came to Northwestern University in 2009, attracted by the University’s reputation for interdisciplinary research, and within weeks was paired up with Mirkin to tackle the difficult problem of developing better treatments for glioblastoma.
Help is critical for patients with GBM: The median survival rate is 14 to 16 months, and approximately 16,000 new cases are reported in the U.S. every year.
In their research partnership, Mirkin had the perfect tool to tackle the deadly cancer: spherical nucleic acids (SNAs), new globular forms of DNA and RNA, which he had invented at Northwestern in 1996, and which are nontoxic to humans. The nucleic acid sequence is designed to match the target gene.
And Stegh had the gene: In 2007, he and colleagues identified the gene Bcl2Like12 as one that is overexpressed in glioblastoma tumors and related to glioblastoma’s resistance to conventional therapies.
“My research group is working to uncover the secrets of cancer and, more importantly, how to stop it,” said Stegh, a senior co-author of the study. “Glioblastoma is a very challenging cancer, and most chemo-therapeutic drugs fail in the clinic. The beauty of the gene we silenced in this study is that it plays many different roles in therapy resistance. Taking the gene out of the picture should allow conventional therapies to be more effective.”
Stegh is an assistant professor in the Ken and Ruth Davee Department of Neurology at the Northwestern University Feinberg School of Medicine and an investigator in the Northwestern Brain Tumor Institute.
The power of gene regulation technology is that a disease with a genetic basis can be attacked and treated if scientists have the right tools. Thanks to the Human Genome Project and genomics research over the last two decades, there is an enormous number of genetic targets; having the right therapeutic agents and delivery materials has been the challenge.
“The RNA interfering-based SNAs are a completely novel approach in thinking about cancer therapy,” Stegh said. “One of the problems is that we have large lists of genes that are somehow disregulated in glioblastoma, but we have absolutely no way of targeting all of them using standard pharmacological approaches. That’s where we think nanomaterials can play a fundamental role in allowing us to implement the concept of personalized medicine in cancer therapy.”
Stegh and Mirkin’s drug for GBM is specially designed to target the Bcl2Like12 gene in cancer cells. Key is the nanostructure’s spherical shape and nucleic acid density. Normal (linear) nucleic acids cannot get into cells, but these spherical nucleic acids can. Small interfering RNA (siRNA) surrounds a gold nanoparticle like a shell; the nucleic acids are highly oriented, densely packed and form a tiny sphere. (The gold nanoparticle core is only 13 nanometers in diameter.) The RNA’s sequence is programmed to silence the disease-causing gene.
“The problems posed by glioblastoma and many other diseases are simply too big for one research group to handle,” said Mirkin, who also is the director of Northwestern’s International Institute for Nanotechnology. “This work highlights the power of scientists and engineers from different fields coming together to address a difficult medical issue.”
Mirkin first developed the nanostructure platform used in this study in 1996 at Northwestern, and the technology now is the basis of powerful commercialized and FDA-cleared medical diagnostic tools. This new development, however, is the first realization that the nanostructures injected into an animal naturally find their target in the brain and can deliver an effective payload of therapeutics.
The next step for the therapeutic will be to test it in clinical trials.
The nanostructures used in this study were developed in Mirkin’s lab on the Evanston campus and then used in cell and animal studies in Stegh’s lab on the Chicago campus.
(Source: northwestern.edu)
Stem Cells Engineered to Become Targeted Drug Factories
A group of Brigham and Women’s Hospital, and Harvard Stem Cell Institute researchers, and collaborators at MIT and Massachusetts General Hospital have found a way to use stem cells as drug delivery vehicles.
The researchers inserted modified strands of messenger RNA into connective tissue stem cells—called mesenchymal stem cells—which stimulated the cells to produce adhesive surface proteins and secrete interleukin-10, an anti-inflammatory molecule. When injected into the bloodstream of a mouse, these modified human stem cells were able to target and stick to sites of inflammation and release biological agents that successfully reduced the swelling.
“If you think of a cell as a drug factory, what we’re doing is targeting cell-based, drug factories to damaged or diseased tissues, where the cells can produce drugs at high enough levels to have a therapeutic effect,” said research leader Jeffrey Karp, PhD, a Harvard Stem Cell Institute principal faculty member and Associate Professor at the Brigham and Women’s Hospital, Harvard Medical School, and Affiliate faculty at MIT.
Karp’s proof of concept study, published in the journal Blood, is drawing early interest from biopharmaceutical companies for its potential to target biological drugs to disease sites. While ranked as the top sellers in the drug industry, biological drugs are still challenging to use, and Karp’s approach may improve their clinical application as well as improve the historically mixed, clinical trial results of mesenchymal stem cell-based treatments.
Mesenchymal stem cells have become cell therapy researchers’ tool of choice because they can evade the immune system, and thus are safe to use even if they are derived from another person. To modify the cells with messenger RNA, the researchers used the RNA delivery and cell programming technique that was previously developed in the MIT laboratory of Mehmet Fatih Yanik, PhD. This RNA technique to program cells is harmless, as it does not modify the cells’ genome, which can be a problem when DNA is used (via viruses) to manipulate gene expression.
“This opens the door to thinking of messenger RNA transfection of cell populations as next generation therapeutics in the clinic, as they get around some of the delivery challenges that have been encountered with biological agents,” said Oren Levy, PhD, co-lead author of the study and Instructor of Medicine in Karp’s lab. The study was also co-led by Weian Zhao, PhD, at University of California, Irvine who was previously a postdoctoral fellow in Karp’s lab.
One such challenge with using mesenchymal stem cells is they have a “hit-and-run” effect, since they are rapidly cleared after entering the bloodstream, typically within a few hours or days. The Harvard/MIT team demonstrated that rapid targeting of the cells to the inflamed tissue produced a therapeutic effect despite the cells being rapidly cleared. The scientists want to extend cell lifespan even further and are experimenting with how to use messenger RNA to make the stem cells produce pro-survival factors.
“We’re interested to explore the platform nature of this approach and see what potential limitations it may have or how far we can actually push it,” Zhao said. “Potentially, we can simultaneously deliver proteins that have synergistic therapeutic impacts.”
When Cells ‘Eat’ Their Own Power Plants; Pitt Scientists Solve Mystery of Basic Cellular Process
A mix of serendipity and dogged laboratory work allowed a diverse team of University of Pittsburgh scientists to report in the Oct. 1 issue of Nature Cell Biology that they had solved the mystery of a basic biological function essential to cellular health.
By discovering a mechanism by which mitochondria – tiny structures inside cells often described as “power plants” – signal that they are damaged and need to be eliminated, the Pitt team has opened the door to potential research into cures for disorders such as Parkinson’s disease that are believed to be caused by dysfunctional mitochondria in neurons.
"It’s a survival process. Cells activate to get rid of bad mitochondria and consolidate good mitochondria. If this process succeeds, then the good ones can proliferate and the cells thrive," said Valerian Kagan, Ph.D., D.Sc., a senior author on the paper and professor and vice chair of the Pitt Graduate School of Public Health’s Department of Environmental and Occupational Health. "It’s a beautiful, efficient mechanism that we will seek to target and model in developing new drugs and treatments."
Dr. Kagan, who, as a recipient of a Fulbright Scholar grant, currently is serving as visiting research chair in science and the environment at McMaster University in Ontario, Canada, likened the process to cooking a Thanksgiving turkey.
"You put the turkey in the oven and the outside becomes golden, but you can’t just look at it to know it’s ready. So you put a thermometer in, and when it pops up, you know you can eat it," he said. "Mitochondria give out a similar ‘eat me’ signal to cells when they are done functioning properly."
Cardiolipins, named because they were first found in heart tissue, are a component on the inner membrane of mitochondria. When a mitochondrion is damaged, the cardiolipins move from its inner membrane to its outer membrane, where they encourage the cell to destroy the entire mitochondrion.
However, that is only part of the process, says Charleen T. Chu, M.D., Ph.D., professor and the A. Julio Martinez Chair in Neuropathology in the Pitt School of Medicine’s Department of Pathology, another senior author of the study. “It’s not just the turkey timer going off; it’s a question of who’s holding the hot mitt to bring it to the dining room?” That turns out to be a protein called LC3. One part of LC3 binds to cardiolipin, and LC3 causes a specialized structure to form around the mitochondrion to carry it to the digestive centers of the cell.
The research arose nearly a decade ago when Dr. Kagan had a conversation with Dr. Chu at a research conference. Dr. Chu, who studies autophagy, or “self-eating,” in Parkinson’s disease, was seeking a change on the mitochondrial surface that could signal to LC3 to bring in the damaged organelle for recycling. It turned out they were working on different sides of the same puzzle.
Together with Hülya Bayır, M.D., research director of pediatric critical care medicine, Children’s Hospital of Pittsburgh of UPMC and professor, Pitt’s Department of Critical Care Medicine, and a team of nearly two dozen scientists, the three senior authors worked out how the pieces of the mitochondria signaling problem fit together.
Now that they’ve worked out the basic mechanism, Dr. Chu indicates that many more research directions will likely follow.
"There are so many follow-up questions," she said. "What is the process that triggers the cardiolipin to move outside the mitochondria? How does this pathway fit in with other pathways that affect onset of diseases like Parkinson’s? Interestingly, two familial Parkinson’s disease genes also are linked to mitochondrial removal."
Dr. Bayir explained that while this process may happen in all cells with mitochondria, it is particularly important that it functions correctly in neuronal cells because these cells do not divide and regenerate as readily as cells in other parts of the body.
"I think these findings have huge implications for brain injury patients," she said. "The mitochondrial ‘eat me’ signaling process could be a therapeutic target in the sense that you need a certain level of clearance of damaged mitochondria. But, on the other hand, you don’t want the clearing process to go on unchecked. You must have a level of balance, which is something we could seek to achieve with medications or therapy if the body is not able to find that balance itself."
(Source: upmc.com)
Sheep’s mucosa shows the way to more effective medicine for severe neurological diseases
New Danish/Italian research shows how medicine for the brain can be absorbed through the nose. This paves the way to more effective treatment of neurological diseases like Alzheimer’s and tumors in the brain.
A big challenge in medical science is to get medicine into the brain when treating patients with neurological diseases. The brain will do everything to keep foreign substances out and therefore the brains of neurological patients fight a constant, daily battle to throw out the medicine prescribed to help the patients.
The problem is the so-called blood-brain barrier, which prevents the active substances in medicine from travelling from the blood into the brain.
"The barrier is created because there is extremely little space between the cells in the brain’s capillar walls. Only very small molecules can enter through these openings and become active in the brain. And for the substances which finally get in, a new problem arises: The brain will do anything to throw them out again", explains assistant professor, Massimiliano di Cagno from in the Department of Physics, Chemistry and Pharmacy.
On this background science is looking for alternative pathways to the brain - and the nose is a candidate receiving much attention. From cocaine abusers it is well known that a substance can be absorbed through the nose and reach the brain extremely effective.
"It is very interesting to investigate if medical drugs can do the same", says di Cagno.
In recent years research has shown that it can be a very good idea to send medicine to the brain via the nose. The medicine can be sprayed into the nose and absorbed through the olfactory bulb, which is positioned at the front of the underside of the brain. Once the medicine passes the olfactory bulb there is direct access to the brain.
But there are many challenges to be solved before patients can be prescribed medication to be taken nasally.
"One of the biggest challenges is getting the olfactory bulb to absorb the substances aimed for the brain", explains di Cagno.
Together with Barbara Luppi from the University of Bologna in Italy he therefore investigated how to improve access to the olfactory bulb.
"It’s all done at nano-level, and the challenge is to find the vehicles that can transport the required medicine to the brain. In our attempts to come up with efficient vehicles we now point at some special liposomes and polymers that can bring an active substance to the olfactory bulb more than 2-3 times more efficiently than when using the standard techniques", explains di Cagno.
Liposomes are small spheres of fat, which is often used to protect active substance and carry them into the body. Polymers are long molecules that can be attached to the liposomes so that they can be made to look like water and thus not be rejected by the body’s immune system.
The improved efficiency is very important for the development of future medicines for neurological diseases. Today a pill has to contain millions of times more active ingredients than the brain needs to fight the disease. But because the blood-brain barrier is so effective and the brain so good at throwing foreign substances out, you have to send an extreme amount of active substances towards the brain.
"In a pill patients receive extremely more medicine than they need, and when we talk about medicines with severe and unpleasant side effects, it is not good. It is therefore very important that we get better at delivering exactly the amount of active substances needed - and no more", says di Cagno.
The new liposomes and polymers from his and Barbara Luppi’s work can not only carry the active ingredients efficiently through the slimy mucosa of a nose, so that they can reach the olfactory bulb. They can also do it over a longer time.
"We want to develop a vehicle that can release the active ingredients over a long time, over many hours, so the patients do not have to spray their nose too many times a day. In our experiments we still saw active substances being released after three hours, and we are very happy with that. One must remember that the nasal mucosa is constantly working to remove foreign objects and substances", says di Cagno.
The researchers performed their tests on the mucous membranes (mucosa) of sheep. Sheep and human mucosa and the mucinous secretions it produces in the nose are very similar. The sheep’s mucosa were cleaned, distributed on a tissue and then stretched over a container. In the container the researchers placed an active substance, hydrocortisone, that had been put inside different kinds of vehicles. After this the researchers observed how effectively and for how long time the various vehicles transported the hydrocortisone through the mucosa.
(Source: sdu.dk)
Breakthrough Offers First Direct Measurement of Spinal Cord Myelin in Multiple Sclerosis
Real-time Imaging Technique Provides Essential Molecular Picture of Protective Nerve Sheath
Researchers have made an exciting breakthrough – developing a first-of-its-kind imaging tool to examine myelin damage in multiple sclerosis (MS). An extremely difficult disease to diagnose, the tool will help physicians diagnose patients earlier, monitor the disease’s progression, and evaluate therapy efficacy.
Case Western Reserve University School of Medicine scientists have developed a novel molecular probe detectable by positron emission tomography (PET) imaging. The new molecular marker, MeDAS, offers the first non-invasive visualization of myelin integrity of the entire spinal cord at the same time, as published today in an article in the Annals of Neurology.
“While MS originates in the immune system, the damage occurs to the myelin structure of the central nervous system. Our discovery brings new hope to clinicians who may be able to make an accurate diagnosis and prognosis in as little as a few hours compared to months or even years,” said Yanming Wang, PhD, senior author of study and associate professor of radiology at Case Western Reserve University School of Medicine. “Because of its shape and size, it is particularly difficult to directly detect myelin damage in the spinal cord; this is the first time we have been able to image its function at the molecular level.”
As the most common acquired autoimmune disease currently affecting more than two million people worldwide, MS is characterized by destruction of myelin, the membrane that protects nerves. Once damaged, it inhibits the nerves’ ability to transmit electrical impulses, causing cognitive impairment and mobility dysfunction. So far, there is no cure for MS, therapies are only available that modify the symptoms.
In addition to its role in monitoring the effects of myelin-repair drugs currently under development, the new imaging tool offers a real-time quantitative clinical diagnosis of MS. A long lag exists between the onset of disease, physical symptoms in the patient and diagnosis via behavioral testing and magnetic resonance imaging (MRI). The lesions, or plaques, as detected by a MRI in the brain and spinal cord are not myelin specific and thus poorly associated with a patient’s disease severity or progression. There is an urgent need to find a new imaging marker that correlates with a patient’s pathology.
“This discovery has open the door to develop new drugs that can truly restore nerve function, not just modify the symptoms,” said Robert Miller, PhD, co-author on the study, vice president for research for Case Western Reserve and the Allen C. Holmes Professor of Neurological Diseases at the School of Medicine. “A cure for MS requires both repairing myelin and a tool to measure the mechanism.”
For the past 20 years, Miller’s lab has been working tirelessly to create new myelin-repair therapies that would restore nerve function. Successful translation of new drugs from animal studies to human clinical trials is contingent upon researchers’ ability to measure and evaluate the effectiveness of a therapy.
Created by Wang’s laboratory, the MeDAS molecular probe works like a homing device. Injected into the body intravenously, it is programmed to seek out and bind only to myelin in the central nervous system, i.e., the brain, spinal cord and optic nerves. A positron-emitting radioisotope label on the molecule allows a PET scanner to detect the targets and quantify their intensity and location. The data can then be reconstructed into an image as shown in the article: http://onlinelibrary.wiley.com/doi/10.1002/ana.23965/abstract.
“This is an indispensable tool to help find a new way to treat MS down the road” said Chunying Wu, PhD, first author of the study and instructor of radiology at Case Western Reserve. “It can also be used as a platform technology to unlock the mysteries of other myelin related diseases such as spinal cord injury.”
(Source: casemed.case.edu)
Propofol Discovery May Aid Development of New Anesthetics
Researchers at Washington University School of Medicine in St. Louis and Imperial College London have identified the site where the widely used anesthetic drug propofol binds to receptors in the brain to sedate patients during surgery.
Until now, it hasn’t been clear how propofol connects with brain cells to induce anesthesia. The researchers believe the findings, reported online in the journal Nature Chemical Biology, eventually will lead to the development of more effective anesthetics with fewer side effects.
“For many years, the mechanisms by which anesthetics act have remained elusive,” explained co-principal investigator Alex S. Evers, MD, the Henry E. Mallinckrodt Professor and head of the Department of Anesthesiology at Washington University. “We knew that intravenous anesthetics, like propofol, act on an important receptor on brain cells called the GABA-A receptor, but we didn’t really know exactly where they bound to that receptor.”
Propofol is a short-acting anesthetic often used in patients having surgery. It wears off quickly and is less likely to cause nausea than many other anesthetics. But the drug isn’t risk-free. Its potentially dangerous side effects include lowering blood pressure and interfering with breathing.
In an attempt to understand how propofol induces anesthesia during surgery, scientists have tried to identify its binding site within the gamma-aminobutyric acid type A (GABA-A) receptor on brain cells. Activating these receptors — with propofol, for example — depresses a cell’s activity.
Researchers have altered the amino acids that make up the GABA-A receptor in attempts to find propofol’s binding site, but Evers said those methods couldn’t identify the precise site with certainty.
“In previous work to directly identify anesthetic binding sites, GABA-A receptors had to be extracted from membranes and purified prior to performing the binding studies,” he said. “Our method allowed us to study propofol binding to the intact receptor in its native membrane environment.”
Having developed the techniques to analyze the interactions between anesthetics and GABA-A receptors in their native environment, Evers’ laboratory teamed up with a group at Imperial College that had been taking the same approach. Led by Nicholas P. Franks, PhD, professor of biophysics and anaesthetics, the group has spent years creating a photoanalogue of propofol that both behaves in precisely the same way as propofol and contains a labeling group that permanently attaches to its binding site on the GABA-A receptor when exposed to a specific wavelength of light.
In creating the analogue of propofol, it’s as if the researchers put a tiny hook onto the molecule so that when it binds to the GABA-A receptor, it grabs onto the receptor and won’t let go.
“Normally, an anesthetic drug binds to the GABA-A receptor transiently,” Franks explained. “But for the purposes of this research, we wanted to create an analogue that behaved exactly like propofol except that we could activate this chemical hook to permanently bind the drug to the receptor. The next step was then to extract the receptor, cut it into pieces and identify the precise piece of the protein where the propofol analogue had attached to the receptor. This was the tricky step that the Evers group at Washington University had perfected.”
Evers and Franks believe this technique has implications beyond propofol and other anesthetics.
“Anesthetics have desirable effects — they induce anesthesia, for example — but they also have undesirable effects,” Evers said. “Propofol can lower blood pressure or interfere with breathing, for example. By understanding precisely what the binding sites look like on the proteins that induce those potential problems, we eventually hope to design and select for drugs that have the benefits we want without dangerous side effects.”
Using the techniques they have developed, Evers and Franks now plan to identify binding sites of other anesthetic agents. They believe their approach also can be used to study other types of drugs, such as psychiatric agents and anti-seizure drugs.
Virginia Tech to Host Neuroscience Workshop in Switzerland
Neuroscientists will discuss cognition, computation, decisions
Nearly two dozen of the world’s leading neuroscientists will gather in Switzerland next month to share their latest findings on the mysteries of how the brain processes information and makes decisions.
The Virginia Tech Carilion Research Institute European–U.S. Workshop on the Neuroscience of Cognition, Computation, and Decisions will be held at Virginia Tech’s Center for European Studies and Architecture at Riva San Vitale in Ticino on Oct. 16 to Oct. 18.
“We have two principal goals for this intensive workshop,” said Michael Friedlander, associate provost for health sciences at Virginia Tech and executive director of the Virginia Tech Carilion Research Institute. “First, we want to identify new and powerful integrated approaches to bridge multiple levels of understanding brain function. We are also hoping to lay the foundations for pioneering innovative and disruptive approaches to transcending disciplines and technologies across teams of leading European brain researchers and Virginia Tech Carilion Research Institute neuroscientists.”
The workshop will convene 10 neuroscientists from the institute and 13 neuroscientists from prominent brain-research institutions in five European countries, includinbg the Centre National de la Recherche Scientifique and École Polytechnique in France; the Central Institute of Mental Health Mannheim, Freie Universität Berlin, the Max Planck Institute for Biological Cybernetics, the Max Planck Institute for Human Development, and the University of Heidelberg in Germany; the International School for Advanced Studies in Trieste, Italy; École Polytechnique Fédérale de Lausanne, ETH Zürich, and the University of Zurich in Switzerland; and University College London in the United Kingdom.
Workshop participants will address emerging views of how neuronal and synaptic networks in the brain assemble, process, store, and access information and how large-scale networks of interconnected neurons perform in humans and other mammals. The participants will also consider the functional architecture that underlies the brain’s decision-making capacity, the neural basis of social interactions, the effects of the environment on information processing, and the consequences of a range of disorders on the function of the human brain.
Participants will share their newest discoveries in multiple sessions of several speakers each, followed by in-depth discussions to identify congruent perspectives and converging insights from multiple disciplines.
The discoveries will represent a broad array of technological and conceptual approaches, including analysis of detailed structural and functional properties of individual neurons and synaptic networks obtained with powerful electrophysiological, genetic, and optical imaging methods; functional brain imaging and behavioral studies in individuals and groups of interacting humans; and computational analysis and modeling of brain function and behavior.
Additional experts will address economics and game theory applications to human brain function and behavior in health and in disease; analysis of development, aging, and educational interventions on brain function; and the modulation of brain function acutely and over time in health and in various disorders that affect behavior, neural information processing, and decision-making.
“This workshop is taking place at a confluence of important national and international milestones in brain research in both Europe and the United States,” Friedlander said. “The Blue Brain Project in Europe represents a major international coalition to support large-scale, detailed analysis of the circuitry of the brain, while in the United States, President Barack Obama’s BRAIN Initiative will support innovative new approaches to high-resolution, large-scale functional mapping of the brain. We’re hoping to harness the wisdom of experts on both continents to develop new approaches and better technologies for diagnosing and treating neurological and psychiatric disorders that affect people worldwide.”