Posts tagged science
Articles and news from the latest research reports.
New Non-Invasive Technique Controls the Size of Molecules Penetrating the Blood-Brain Barrier
A new technique developed by Elisa Konofagou, professor of biomedical engineering and radiology at Columbia Engineering, has demonstrated for the first time that the size of molecules penetrating the blood-brain barrier (BBB) can be controlled using acoustic pressure—the pressure of an ultrasound beam—to let specific molecules through. The study was published in the July issue of the Journal of Cerebral Blood Flow & Metabolism.
“This is an important breakthrough in getting drugs delivered to specific parts of the brain precisely, non-invasively, and safely, and may help in the treatment of central nervous system diseases like Parkinson’s and Alzheimer’s,” says Konofagou, whose National Institutes of Health Research Project Grant (R01) funding was just renewed for another four years for an additional $2.22 million. The award is for research to determine the role of the microbubble in controlling both the efficacy and safety of drug safety through the BBB with a specific application for treating Parkinson’s disease.
Most small—and all large—molecule drugs do not currently penetrate the blood-brain barrier that sits between the vascular bed and the brain tissue. “As a result,” Konofagou explains, “all central nervous system diseases remain undertreated at best. For example, we know that Parkinson’s disease would benefit by delivery of therapeutic molecules to the neurons so as to impede their slow death. But because of the virtually impermeable barrier, these drugs can only reach the brain through direct injection and that requires anesthesia and drilling the skull while also increasing the risk of infection and limiting the number of sites of injection. And transcranial injections rarely work—only about one in ten is successful.”
Focused ultrasound in conjunction with microbubbles—gas-filled bubbles coated by protein or lipid shells—continues to be the only technique that can permeate the BBB safely and non-invasively. When microbubbles are hit by an ultrasound beam, they start oscillating and, depending on the magnitude of the pressure, continue oscillating or collapse. While researchers have found that focused ultrasound in combination with microbubble cavitation can be successfully used in the delivery of therapeutic drugs across the BBB, almost all earlier studies have been limited to one specific-sized agent that is commercially available and widely used clinically as ultrasound contrast agents. Konofagou and her team were convinced there was a way to induce a size-controllable BBB opening, enabling a more effective method to improve localized brain drug delivery.
Konofagou targeted the hippocampus, the memory center of the brain, and administered different-sized sugar molecules (Dextran). She found that higher acoustic pressures led to larger molecules accumulating into the hippocampus as confirmed by fluorescence imaging. This demonstrated that the pressure of the ultrasound beam can be adjusted depending on the size of the drug that needs to be delivered to the brain: all molecules of variant sizes were able to penetrate the opened barrier but at distinct pressures, i.e., small molecules at lower pressures and larger molecules at higher pressures.
“Through this study, we’ve been able to show, for the first time, that we can control the BBB opening size through the use of acoustic pressure,” says Konofagou. “We’ve also learned much more about the physical mechanisms associated with the trans-BBB delivery of different-sized agents, and understanding the BBB mechanisms will help us to develop agent size-specific focused ultrasound treatment protocols.”
Konofagou and her Ultrasound Elasticity Imaging Laboratory team plan to continue to work on the treatment of Alzheimer’s and Parkinson’s in a range of models, and hope to test their technique in clinical trials within the next five years.
“It is frightening to think that in the 21st century we still have no idea how to treat most brain diseases,” Konofagou adds. “But we’re really excited because we now have a tool that could potentially change the current dire predictions that come with a neurological disorder diagnosis.”
(Source: engineering.columbia.edu)
Stuck in neutral: brain defect traps schizophrenics in twilight zone
People with schizophrenia struggle to turn goals into actions because brain structures governing desire and emotion are less active and fail to pass goal-directed messages to cortical regions affecting human decision-making, new research reveals.
Published in Biological Psychiatry, the finding by a University of Sydney research team is the first to illustrate the inability to initiate goal-directed behaviour common in people with schizophrenia.
The finding may explain why people with schizophrenia have difficulty achieving real-world goals such as making friends, completing education and finding employment.
"The apparent lack of motivation in schizophrenic patients isn’t because they lack goals or don’t enjoy rewards and pleasure," says the University of Sydney’s Dr Richard Morris, the study’s lead author.
"They enjoy as many experiences as other people, including food, movies and scenes of natural beauty.
"What appears to block them are specific brain deficits that prevent them from converting their desires and goals into choices and behaviour."
Using a control group research design, the researchers used a two-prong approach to reveal how and why schizophrenics fail to convert their preferences into congruent choices.
First, using a series of experiments involving choosing between different snack food rewards, experimenters revealed that:
- schizophrenic subjects had a liking for snack foods equivalent to healthy adults
- when researchers reduced the value of one of the snacks, both subjects and healthy adults subsequently preferred different snacks, as expected
- surprisingly, schizophrenic subjects had major difficulty choosing their preferred snack when provided with a choice between their preferred snack and the devalued snack.
Second, researchers used functional magnetic resonance imaging (fMRI) to measures brain activity while study subjects performed learning tasks involving snack foods.
This technique relies on the fact that cerebral blood flow and neuronal activity are coupled. When an area of the brain is in use, bloodflow to that region increases, thereby indicating neural activity. This neural activity can be presented graphically by colour-coding the strength of activation across the brain or in specific brain regions. The technique can localise neural activity to within millimetres.
Functional MRI results revealed the following:
- schizophrenic subjects had normal neural activity in the brain region responsible for decision-making (prefrontal cortex)
- among schizophrenic subjects, brain regions responsible, in part, for controlling actions and choice (the caudate) had far lower neural activity than in healthy subjects
- lower neural activity in the caudate regions was correlated with the difficulty that schizophrenic subjects’ had applying their food preferences to obtain future snack foods.
"Pathology in the caudate and associated brain regions may prevent schizophrenic subjects from properly evaluating their desires then transmitting that information to guide their behavior," says Dr Morris.
"This means that desires and goals are intact in people with schizophrenia, however they have difficulty choosing the right course of action to achieve those goals.
"This failure to integrate desire with action means people with schizophrenia are stuck in limbo, wanting a normal life but unable to take the necessary steps to achieve it."
Schizophrenia affects one per cent of people worldwide, including in Australia.
However so-called “poor motivation” in schizophrenia is a major economic concern because it is not treated by current medicines, and often means patients fail to finish their education or hold a full-time job.
(Source: sydney.edu.au)
Researchers develop strategy to combat genetic ALS, FTD
A team of researchers at Mayo Clinic and The Scripps Research Institute in Florida have developed a new therapeutic strategy to combat the most common genetic risk factor for the neurodegenerative disorders amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease) and frontotemporal dementia (FTD). In the Aug. 14 issue of Neuron, they also report discovery of a potential biomarker to track disease progression and the efficacy of therapies.
The scientists developed a small-molecule drug compound to prevent abnormal cellular processes caused by a mutation in the C9ORF72 gene. The findings come on the heels of previous discoveries by Mayo investigators that the C9ORF72 mutation produces an unusual repetitive genetic sequence that causes the buildup of abnormal RNA in brain cells and spinal cord.
While toxic protein clumps have long been implicated in neurodegeneration, this new strategy takes aim at abnormal RNA, which forms before toxic proteins in C9ORF72-related disorders (c9FTD/ALS). “Our study shows that toxic RNA produced in people with the c9FTD/ALS mutation is indeed a viable drug target,” says the study’s co-senior investigator, Leonard Petrucelli, Ph.D., a molecular neuroscientist at Mayo Clinic in Florida.
The compound, which was tested in cell culture models of c9FTD/ALS, bound to and blocked RNA’s ability to interact with other key proteins, thereby preventing the formation of toxic RNA clumps and “c9RAN proteins” that results from a process called repeat-associated non-ATG (RAN) translation.
The researchers also discovered that c9RAN proteins produced by the abnormal RNA can be measured in the spinal fluid of ALS patients. They are now evaluating whether these proteins are also present in spinal fluid of patients diagnosed with FTD. Although ALS primarily affects motor neurons leading to impaired mobility, speech, swallowing, and respiratory function and FTD affects brain regions that support higher cognitive function, some patients have symptoms of both disorders.
“Development of a readily accessible biomarker for the c9FTD/ALS mutation may aid not only diagnosis of these disorders and allow for tracking disease course in patients, but it could provide a more direct way to evaluate the response to experimental treatments,” says co-author Kevin Boylan, M.D., medical director of the Mayo Jacksonville ALS Center, the only ALS Certified Center of Excellence in Florida.
For example, a decrease in the levels of c9RAN proteins in response to treatment would suggest that a drug is having a desired effect. “The potential of this biomarker discovery is very exciting — even if we are in early days of development of such a test,” he says.
Since ALS is usually fatal two to five years after diagnosis and there is currently no effective treatment for FTD, these landmark findings offer the possibility of both improved diagnosis and treatment for up to 40 percent of all patients with familial (inherited) ALS and up to 25 percent of patients with familial FTD, says Dr. Boylan.
“One of the most exciting aspects of these studies has, in my opinion, been the seamless collaboration of our Florida biosciences institutes — Scripps and Mayo. Our collective biological and chemical expertise made this research possible,” says the other co-senior investigator, Mathew Disney, Ph.D., a professor of chemistry at Scripps Florida.
Dr. Disney and his group studied the structure of the RNA that resulted from the C9ORF72 mutation, and then designed the lead small-molecules. The Mayo team developed the patient-derived cell models to test the compounds in. Both teams then worked together to show that the lead agent’s mode of action was targeting the toxic RNA.
Scientists use lasers to control mouse brain switchboard
Ever wonder why it’s hard to focus after a bad night’s sleep? Using mice and flashes of light, scientists show that just a few nerve cells in the brain may control the switch between internal thoughts and external distractions. The study, partly funded by the National Institutes of Health, may be a breakthrough in understanding how a critical part of the brain, called the thalamic reticular nucleus (TRN), influences consciousness.
“Now we may have a handle on how this tiny part of the brain exerts tremendous control over our thoughts and perceptions,” said Michael Halassa, M.D., Ph.D., assistant professor at New York University’s Langone Medical Center and a lead investigator of the study. “These results may be a gateway into understanding the circuitry that underlies neuropsychiatric disorders.”
The TRN is a thin layer of nerve cells on the surface of the thalamus, a center located deep inside the brain that relays information from the body to the cerebral cortex. The cortex is the outer, multi-folded layer of the brain that controls numerous functions, including one’s thoughts, movements, language, emotions, memories, and visual perceptions. TRN cells are thought to act as switchboard operators that control the flow of information relayed from the thalamus to the cortex.
“The future of brain research is in studying circuits that are critical for brain health and these results may take us a step further,” said James Gnadt, Ph.D., program director at NIH’s National Institute Neurological Disorders and Stroke (NINDS), which helped fund the study. “Understanding brain circuits at the level of detail attained in this study is a goal of the President’s Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative.”
To study the circuits, the researchers identified TRN cells that send inhibitory signals to parts of the thalamus known to relay visual information to the cortex. Using a technique known as multi-electrode recordings, they showed that sleep and concentration affected these cells in opposite ways.
They fired often when the mice were asleep, especially during short bursts of simultaneous brain cell activity called sleep spindles. These activity bursts briefly widen electrical brain wave traces making them look like spindles, the straight spikes with rounded bottoms used to make yarn. In contrast, the cells fired infrequently when the mice were tasked with using visual cues to find food. The results suggested that these cells blocked visual information from reaching the cortex during sleep and allowed its transmission when the mice were awake and attentive.
For Dr. Halassa, a practicing psychiatrist who treats schizophrenia, these surprising results may provide fundamental insights into how the brain controls information transmission, a process that is disrupted in patients with neuropsychiatric disorders. Previous studies suggested that people who experienced more spindles while sleeping were less susceptible to being disturbed by outside noises. Moreover, people with schizophrenia and autism spectrum disorder may experience fewer spindles.
“Spindles may be peepholes into the mysteries of these disorders,” said Dr. Halassa.
To test this idea, the researchers used optogenetics, a technique that introduces light-sensitive molecules into nerve cells. This allowed them to precisely control the firing patterns of visual TRN cells with flashes of laser light. The experiments were performed in well-rested as well as sleep-deprived mice. Similar to what is seen in humans, sleep deprivation can disrupt the ability of mice to focus and block out external distractions.
Well-rested mice needed just a second or two to find the food whereas sleep-deprived mice took longer, suggesting that lack of sleep had detrimental effects on their ability to focus. When the researchers used flashes of laser light to inhibit the firing of optogenetically engineered visual TRN cells in sleep-deprived mice, the mice found the food faster. In contrast, if they used optogenetics to induce sleep-like firing patterns in well-rested mice, then the mice took longer to find food.
“It’s as if with a flick of a switch we could alter the mental states of the mice and either mimic or cure their drowsiness,” said Dr. Halassa.
In a parallel set of experiments the researchers found neighbors of the visual TRN cells had very different characteristics. These neighboring cells control the flow of information to the cortex from limbic brain regions, which are involved with memory formation, emotions and arousal. The cells fired very little during sleep and instead were active when the mice were awake. Dr. Halassa thinks that their firing pattern may be important for the strengthening of new memories that often occurs during sleep. Combined, the results suggest that the TRN is divided into sub-networks that oversee discrete mental states. The researchers think understanding the sub-networks is an initial step in thoroughly exploring the role of the TRN in brain disorders.
Memories of Errors Foster Faster Learning
Using a deceptively simple set of experiments, researchers at Johns Hopkins have learned why people learn an identical or similar task faster the second, third and subsequent time around. The reason: They are aided not only by memories of how to perform the task, but also by memories of the errors made the first time.
“In learning a new motor task, there appear to be two processes happening at once,” says Reza Shadmehr, Ph.D., a professor in the Department of Biomedical Engineering at the Johns Hopkins University School of Medicine. “One is the learning of the motor commands in the task, and the other is critiquing the learning, much the way a ‘coach’ behaves. Learning the next similar task goes faster, because the coach knows which errors are most worthy of attention. In effect, this second process leaves a memory of the errors that were experienced during the training, so the re-experience of those errors makes the learning go faster.”
Shadmehr says scientists who study motor control — how the brain pilots body movement — have long known that as people perform a task, like opening a door, their brains note small differences between how they expected the door to move and how it actually moved, and they use this information to perform the task more smoothly next time. Those small differences are scientifically termed “prediction errors,” and the process of learning from them is largely unconscious.
The surprise finding in the current study, described in Science Express on Aug. 14, is that not only do such errors train the brain to better perform a specific task, but they also teach it how to learn faster from errors, even when those errors are encountered in a completely different task. In this way, the brain can generalize from one task to another by keeping a memory of the errors.
To study errors and learning, Shadmehr’s team put volunteers in front of a joystick that was under a screen. Volunteers couldn’t see the joystick, but it was represented on the screen as a blue dot. A target was represented by a red dot, and as volunteers moved the joystick toward it, the blue dot could be programmed to move slightly off-kilter from where they pointed it, creating an error. Participants then adjusted their movement to compensate for the off-kilter movement and, after a few more trials, smoothly guided the joystick to its target.
In the study, the movement of the blue dot was rotated to the left or the right by larger or smaller amounts until it was a full 30 degrees off from the joystick’s movement. The research team found that volunteers responded more quickly to smaller errors that pushed them consistently in one direction and less to larger errors and those that went in the opposite direction of other feedback. “They learned to give the frequent errors more weight as learning cues, while discounting those that seemed like flukes,” says David Herzfeld, a graduate student in Shadmehr’s laboratory who led the study.
The results also have given Shadmehr a new perspective on his after-work tennis hobby. “I’m much better in my second five minutes of playing tennis than in my first five minutes, and I always assumed that was because my muscles had warmed up,” he says. “But now I wonder if warming up is really a chance for our brains to re-experience error.”
“This study represents a significant step toward understanding how we learn a motor skill,” says Daofen Chen, Ph.D., a program director at the National Institute of Neurological Disorders and Stroke. “The results may improve movement rehabilitation strategies for the many who have suffered strokes and other neuromotor injuries.”
The next step in the research, Shadmehr says, will be to find out which part of the brain is responsible for the “coaching” job of assigning weight to different types of error.
Awake within a dream: lucid dreamers show greater insight in waking life
People who are aware they are asleep when they are dreaming have better than average problem-solving abilities, new research has discovered.
Experts from the University of Lincoln, UK, say that those who experience ‘lucid dreaming’ – a phenomena where someone who is asleep can recognise that they are dreaming – can solve problems in the waking world better than those who remain unaware of the dream until they wake up.
The concept of lucid dreaming was explored in the 2010 film Inception, where the dreamers were able to spot incongruities within their dream. It is thought some people are able to do this because of a higher level of insight, meaning their brains detect they are in a dream because events would not make sense otherwise. This cognitive ability translates to the waking world when it comes to finding the solution to a problem by spotting hidden connections or inconsistencies, researchers say.
The research was carried out by Dr Patrick Bourke, Senior Lecturer at the Lincoln School of Psychology and his student Hannah Shaw. It is the first empirical study demonstrating the relationship between lucid dreaming and insight.
He said: “It is believed that for dreamers to become lucid while asleep, they must see past the overwhelming reality of their dream state, and recognise that they are dreaming.
“The same cognitive ability was found to be demonstrated while awake by a person’s ability to think in a different way when it comes to solving problems.”
The study examined 68 participants aged between 18 and 25 who had experienced different levels of lucid dreaming, from never to several times a month. They were asked to solve 30 problems designed to test insight. Each problem consisted of three words and a solution word.
Each of the three words could be combined with the solution word to create a new compound word.
For example with the words ‘sand’, ‘mile’ and ‘age’, the linking word would be ‘stone’.
Results showed that frequent lucid dreamers solved 25 per cent more of the insight problems than the non-lucid dreamers.
Miss Shaw, who conducted the research as part of her undergraduate dissertation, said the ability to experience lucid dreams is something that can be learned. “We aren’t entirely sure why some people are naturally better at lucid dreaming than others, although it is a skill which can be taught,” said Hannah.
“For example you can get into the habit of asking yourself “is this a dream?”. If you do this during the day when you are awake and make it a habit then it can transfer to when you are in a dream.”
(Source: lincoln.ac.uk)
Passengers who survived terrifying Air Transat flight in 2001, help psychologists uncover new clues about post-traumatic stress vulnerability
An extraordinary opportunity to study memory and post-traumatic stress disorder (PTSD) in a group of Air Transat passengers who experienced 30 minutes of unimaginable terror over the Atlantic Ocean in 2001 has resulted in the discovery of a potential risk factor that may help predict who is most vulnerable to PTSD.
The study, led by researchers at Baycrest Health Sciences, is published online this week in the journal Clinical Psychological Science – ahead of print publication. It is the first to involve detailed interviews and psychological testing in individuals exposed to the same life-threatening traumatic event. By necessity, other trauma studies involve heterogeneous events as experienced in different situations.
This opportunity was enhanced by the fact that one of the researchers, Dr. Margaret McKinnon, was a passenger on the plane. Heading off on her honeymoon in late August 2001, Dr. McKinnon’s flight departed Toronto for Lisbon, Portugal with 306 passengers and crew on board. Mid way over the Atlantic Ocean, the plane suddenly ran out of fuel. Everyone onboard was instructed to prepare for an ocean ditching, which included a countdown to impact, loss of on-board lighting and cabin de-pressurization. About 25 minutes into the emergency, the pilot located a small island military base in the Azores and glided the aircraft to a rough landing with no loss of life and few injuries.
“Imagine your worst nightmare – that’s what it was like,” said Dr. McKinnon, who initiated the study as a postdoctoral fellow at Baycrest’s Rotman Research Institute. She is now a clinician-scientist at St. Joseph’s Healthcare Hamilton and Associate Co-Chair of Research in the Department of Psychiatry and Behavioural Neurosciences at McMaster University in Hamilton.
“This wasn’t just a close call where your life flashes before your eyes in a split second and then everything is okay,” she said. The sickening feeling of “I’m going to die” lasted an excruciating 30 minutes as the plane’s systems shut down.
Following this incident, Dr. McKinnon and her colleagues at Baycrest – including Dr. Daniela Palombo (now a postdoctoral researcher at VA Boston Healthcare System and Boston University School of Medicine) and Dr. Brian Levine (senior scientist at Baycrest’s Rotman Research Institute and the University of Toronto) – recruited 15 passengers to participate in the Baycrest study. Using their knowledge of the moment-to-moment unfolding of events in this disaster, the researchers were able to probe both the quality and accuracy of passengers’ memories for the AT emergency in great detail along with two other events (Sept. 11, 2001 and a neutral event from the same time period) – and relate their findings to the presence or absence of PTSD in those passengers.
Not all passengers on Flight 236 went on to develop PTSD despite experiencing the same “single blow” traumatic event with the threat of imminent death.
The study produced two key findings. First, the Flight 236 passengers showed tremendously enhanced vivid memories of the plane emergency. Although the Baycrest team was not surprised by this, other research has suggested that memory for traumatic events is impoverished. Second, neither the vividness nor accuracy of memory related to who developed PTSD, but those with PTSD recalled a higher number of details external to the main event (i.e. details that were not specific in time, or were repetitions or editorial statements) compared to passengers who did not have PTSD and to healthy controls. This pattern was observed across all events tested, not just the traumatic event, suggesting that it is not just memory for the trauma itself that is related to PTSD, but rather how a person processes memory for events in general.
“What our findings show is that it is not what happened but to whom it happened that may determine subsequent onset of PTSD,” said Dr. Levine, senior author of the study.
This inability to shut out external or semantic details when recalling personally-experienced memories is related to mental control over memory recall, adding to a growing body of evidence that altered memory processing may be a vulnerability factor for PTSD.
A second study, in preparation for publication, involves functional brain imaging of 10 of the passengers from Air Transat Flight 236. The aim is to illuminate the brain mechanisms associated with exposure to this traumatic event.
(Source: baycrest.org)
(Image caption: A cancer cell containing the nanoparticles. The nanoparticles are coloured green, and have entered the nucleus, which is the area in blue. Credit: M Welland)
“Trojan horse” treatment could beat brain tumours
A smart technology which involves smuggling gold nanoparticles into brain cancer cells has proven highly effective in lab-based tests.
A “Trojan horse” treatment for an aggressive form of brain cancer, which involves using tiny nanoparticles of gold to kill tumour cells, has been successfully tested by scientists.
The ground-breaking technique could eventually be used to treat glioblastoma multiforme, which is the most common and aggressive brain tumour in adults, and notoriously difficult to treat. Many sufferers die within a few months of diagnosis, and just six in every 100 patients with the condition are alive after five years.
The research involved engineering nanostructures containing both gold and cisplatin, a conventional chemotherapy drug. These were released into tumour cells that had been taken from glioblastoma patients and grown in the lab.
Once inside, these “nanospheres” were exposed to radiotherapy. This caused the gold to release electrons which damaged the cancer cell’s DNA and its overall structure, thereby enhancing the impact of the chemotherapy drug.
The process was so effective that 20 days later, the cell culture showed no evidence of any revival, suggesting that the tumour cells had been destroyed.
While further work needs to be done before the same technology can be used to treat people with glioblastoma, the results offer a highly promising foundation for future therapies. Importantly, the research was carried out on cell lines derived directly from glioblastoma patients, enabling the team to test the approach on evolving, drug-resistant tumours.
The study was led by Mark Welland, Professor of Nanotechnology at the Department of Engineering and a Fellow of St John’s College, University of Cambridge, and Dr Colin Watts, a clinician scientist and honorary consultant neurosurgeon at the Department of Clinical Neurosciences. Their work is reported in the Royal Society of Chemistry journal, Nanoscale.
“The combined therapy that we have devised appears to be incredibly effective in the live cell culture,” Professor Welland said. “This is not a cure, but it does demonstrate what nanotechnology can achieve in fighting these aggressive cancers. By combining this strategy with cancer cell-targeting materials, we should be able to develop a therapy for glioblastoma and other challenging cancers in the future.”
To date, glioblastoma multiforme (GBM) has proven very resistant to treatments. One reason for this is that the tumour cells invade surrounding, healthy brain tissue, which makes the surgical removal of the tumour virtually impossible.
Used on their own, chemotherapy drugs can cause a dip in the rate at which the tumour spreads. In many cases, however, this is temporary, as the cell population then recovers.
“We need to be able to hit the cancer cells directly with more than one treatment at the same time” Dr Watts said. “This is important because some cancer cells are more resistant to one type of treatment than another. Nanotechnology provides the opportunity to give the cancer cells this ‘double whammy’ and open up new treatment options in the future.”
In an effort to beat tumours more comprehensively, scientists have been researching ways in which gold nanoparticles might be used in treatments for some time. Gold is a benign material which in itself poses no threat to the patient, and the size and shape of the particles can be controlled very accurately.
When exposed to radiotherapy, the particles emit a type of low energy electron, known as Auger electrons, capable of damaging the diseased cell’s DNA and other intracellular molecules. This low energy emission means that they only have an impact at short range, so they do not cause any serious damage to healthy cells that are nearby.
In the new study, the researchers first wrapped gold nanoparticles inside a positively charged polymer, polyethylenimine. This interacted with proteins on the cell surface called proteoglycans which led to the nanoparticles being ingested by the cell.
Once there, it was possible to excite it using standard radiotherapy, which many GBM patients undergo as a matter of course. This released the electrons to attack the cell DNA.
While gold nanospheres, without any accompanying drug, were found to cause significant cell damage, treatment-resistant cell populations did eventually recover several days after the radiotherapy. As a result, the researchers then engineered a second nanostructure which was suffused with cisplatin.
The chemotherapeutic effect of cisplatin combined with the radiosensitizing effect of gold nanoparticles resulted in enhanced synergy enabling a more effective cellular damage. Subsequent tests revealed that the treatment had reduced the visible cell population by a factor of 100 thousand, compared with an untreated cell culture, within the space of just 20 days. No population renewal was detected.
The researchers believe that similar models could eventually be used to treat other types of challenging cancers. First, however, the method itself needs to be turned into an applicable treatment for GBM patients. This process, which will be the focus of much of the group’s forthcoming research, will necessarily involve extensive trials. Further work needs to be done, too, in determining how best to deliver the treatment and in other areas, such as modifying the size and surface chemistry of the nanomedicine so that the body can accommodate it safely.
Sonali Setua, a PhD student who worked on the project, said: “It was hugely satisfying to chase such a challenging goal and to be able to target and destroy these aggressive cancer cells. This finding has enormous potential to be tested in a clinical trial in the near future and developed into a novel treatment to overcome therapeutic resistance of glioblastoma.”
Welland added that the significance of the group’s results to date was partly due to the direct collaboration between nanoscientists and clinicians. “It made a huge difference, as by working with surgeons we were able to ensure that the nanoscience was clinically relevant,” he said. “That optimises our chances of taking this beyond the lab stage, and actually having a clinical impact.”
Researchers reveal weakness in defenses of deadly brain tumor
Glioblastoma is a complex, deadly, and hard-to-treat brain cancer, but Yale School of Medicine researchers may have found the tumor’s Achilles heel.
The researchers report in the Aug. 12 issue of the journal Science Signaling that targeting a protein crucial in the early development of the brain can block multiple signaling pathways implicated in glioblastoma growth. The approach also reduced human tumors in mouse models of the disease.
“In neurodevelopment, this protein (atyptical protein kinase or aPKC) helps regulate proliferation and migration of cells but when active in adults, can cause formation and spread of cancer,” said Sourav Ghosh, assistant professor of neurology and co-senior author of the paper.
About 13,000 people die of primary malignant brain tumors annually in the United States. Glioblastomas are particularly hard to treat because these tumors grow rapidly, spread quickly, and respond poorly to current anti-tumor therapies.
The new study shows that targeting this protein works in several ways. Inhibiting aPKC blocks a signal pathway that is the target of existing glioblastoma therapy. But it also blocks the action of some immune system cells called macrophages, which instead of attacking tumors, actively promote their growth.
“This is exciting because it ends up targeting multiple pathways involved in cancer,” said Carla Rothlin, assistant professor of immunobiology and co-senior author of the paper.
Autism rates steady for two decades
A University of Queensland study has found no evidence of an increase in autism in the past 20 years, countering reports that the rates of autism spectrum disorders (ASDs) are on the rise.
The study, led by Dr Amanda Baxter from UQ’s Queensland Centre for Mental Health Research at the School of Population Health, was a first-of-its-kind analysis of research data from 1990 to 2010.
Dr Baxter said she and her colleagues found that rates had remained steady, despite reports that the prevalence of ASDs was increasing.
“We found that the prevalence of ASDs in 2010 was one in 132 people, which represents no change from 1990,” Dr Baxter said.
“We found that better recognition of the disorders and improved diagnostic criteria explain much of the difference in study findings over time.”
Part of the Global Burden of Disease project, this is the largest study to systematically assess rates and disability caused by ASDs in the community, using data collected from global research findings in the past 20 years.
ASDs are chronic, disabling disorders that stem from problems with brain development.
They affect people from a young age and are among the world’s 20 most disabling childhood conditions.
The study shows that about 52 million children and adults around the globe meet diagnostic criteria for an ASD.
Dr Baxter said researchers hoped the study would help guide health policy and improve support for those with ASD and their families.
“As ASDs cause substantial lifelong health issues, an accurate understanding of the burden of these disorders can inform public health policy as well as help allocate necessary resources for education, housing and employment,” she said.
The study, a collaboration with the University of Leicester and the University of Washington’s Institute for Health Metrics and Evaluation, is published in Psychological Medicine journal.
(Source: uq.edu.au)