Treatment for multiple sclerosis (MS) patients could be revolutionised in ground-breaking trials planned by a Cambridge scientist.
Dr Su Metcalfe, a University of Cambridge senior research associate based at Addenbrooke’s, has won a £150,000 award which will enable her team to proceed to pre-clinical trials in Nanotechnology.
The award is one of only five given out this year worldwide from major pharmaceutical company, Merck Serono, and the first to a UK scientist.
The technology developed for treatment of MS - an incurable autoimmune disease that attacks the central nervous system - by Dr Metcalfe uses tiny ‘smart’ nanoparticles that act as magic bullets to deliver powerful factors known to increase repair of damaged myelin. The key factor is “LIF”, a stem cell protein.
The money from the Merck-Serono’s “Grants for Multiple Sclerosis International” (GMSI) scheme will fund preclinical trials of Metcalfe’s nano-therapeutic device that taps into the body’s natural mechanisms for repair and avoids use of drugs.
“Nanotechnology is now recognised as a key platform for healthcare,” said Dr Metcalfe. “Our ‘smart’ technology allows us to target delivery of molecules able to repair myelin and also reduce inflammation.
“By using a nanoparticle platform where the safety in humans is already confirmed, a hugely important feature for rapid progress towards the clinic, we can now expect to move to clinical trials within three to five years.”
Multiple sclerosis commonly affects young adults and in the UK alone, more than 100,000 people have MS with 2,500 being diagnosed each year.
The disease causes damage to the nerve sheaths, or myelin, which normally insulate the electrical activity of nerve fibres in the brain and spinal cord.
Specific nerves become inflamed and lose function and this disrupts messages from the brain to parts of the body, resulting in early symptoms of MS, such as impaired vision.
The award will link a small team of experts including bioengineer Dr Tarek Fahmy of Yale University who prepares the smart nanoparticles, Professors David Baker and Gavin Giovannoni who lead preclinical and clinical trials in MS at Queen Mary’s University of London, and Dr Anna Williams who works on progressive MS at the University of Edinburgh.
This GMSI project exploits nanotechnology to harness the power of Leukaemia Inhibitory Factor (LIF), a potent stem cell cytokine able to both oppose inflammatory immunity and promote myelin repair - both highly relevant to treatment of MS.
Source: CambridgeNewsUK Copyright © 2014 Local World (02/10/14)
An exercise component of the popular Nintendo Wii video game may help multiple sclerosis patients improve their balance by rewiring their brains, a new study suggests.
No medications exist to preserve balance in MS patients, and some drugs make balance worse, said study lead author Dr. Luca Prosperini, a neurologist at Sapienza University in Rome, Italy.
It appears that patients who use the Wii Balance Board five days a week -- moving to snowboarding or dance games, for example -- may help reduce their risk of falls and boost certain brain connections, possibly because they're coordinating their movements with a figure on a screen, Prosperini said.
There are caveats to the research, however. The study was small, and there's a risk that patients could hurt themselves by falling, although they can play seated rather than stand on the balance board.
"Patients with MS should be encouraged to start using this system only under supervision," Prosperini said. "Once well-trained, they may use it at home."
Multiple sclerosis is a nerve disorder that affects how the brain communicates with the body.
"Balance problems are quite common and arise due to the effects of MS on a number of functions that are important for balance," said Nicholas LaRocca, vice president for health care delivery and policy research with the National Multiple Sclerosis Society. Among other things, MS can disrupt vision, coordination and the body's balancing mechanism, he said.
Patients turn to a variety of strategies to support balance, he said. Canes and orthotic devices (shoe inserts) help some people, and rehabilitation can build strength and coordination. Some patients try electrical muscle stimulation to maintain or regain control of their muscles, he said.
Prosperini was inspired to study a video game treatment for MS when he saw patients in rehabilitation using a balance-boosting system that reminded him of an old Atari video game. Then a commercial about the Wii Balance Board caught his attention. The balance board, shaped a bit like a weight scale, detects a person's movements and allows them to be translated into action on a TV screen.
Prosperini tried to get a grant from Nintendo to support research. The company wasn't interested, he said, but he obtained funding from the Italian MS Society.
His previous research has supported the idea that patients regain balance when they use the Wii Balance Board. The new study aimed to understand what's happening in their brains.
In the new study, published online Aug. 26 in Radiology, 27 MS patients were split into two groups. One group spent three months doing nothing special while the other group played with the Wii Balance Board for 30 to 40 minutes daily, five days a week. Then the groups reversed roles: Those who had done nothing special used the balance board for three months, while the others stopped using it.
Another 15 healthy people tried the system, too.
All participants had specialised MRI scans to detect any physiological changes in the brain.
The researchers found that patients regained some balance, presumably by using the board, and their brains actually changed. Using the video game was tied to improvements in the protective sheath around nerves, leading to better conduction of impulses between the body and brain, Prosperini said.
It's not clear if other kinds of training might also help MS patients regain balance, he said. But video games like those that use the balance board might have similar benefits because they require patients to mimic movements that they see on screen, potentially providing an extra brain boost.
LaRocca, of the MS Society, said the study is valid but has limitations. For one, it's difficult to interpret what the brain changes mean, he said. Also, he added, the research suggests that the improvements in balance aren't permanent, requiring patients to keep at it to make the benefits last.
"Training needs to be ongoing, just like any other form of exercise," LaRocca said.
While the study found an association between the video-game balance board and balance-enhancing brain changes, it did not establish a cause-and-effect relationship. Prosperini said more research is needed, especially since the study was so small.
"There is increasing evidence of the clinical benefit of playing with the balance board, and more in general with highly interactive video games," he said. But researchers don't know enough about why the patients are getting better, he added.
Souce: healthfinder.gov Copyright © 2014 HealthDay (27/08/14)
iPad performance testing in MS(17/06/14)
In the not-too-distant future, patients with multiple sclerosis (MS) may simply strap on an iPad to complete their balance and walking tests, without the need for a technician.
The test results would be automatically uploaded to a clinical or research database, eliminating the chance of human error.
And patients may be doing the tests in the comfort of their own home, eliminating the need to visit a clinic, a boon to those living in rural areas or with mobility issues.
"It's an entirely new way of measuring the clinical impact of MS," said Richard A Rudick, MD, who recently left the Cleveland Clinic Mellen Center for Multiple Sclerosis Treatment and Research in Ohio to become vice president, development sciences, Value-Based Medicine, Biogen Idec."The bottom line on this is a new method to collect, display, aggregate, and analyse neurological performance data that has potential to have a major impact in MS patient care and research."
Dr. Rudick was addressing the 6th Cooperative Meeting of the Consortium of Multiple Sclerosis Centers (CMSC) and the Americas Committee for Treatment and Research In Multiple Sclerosis (ACTRIMS).
The iPad is designed to simulate the standard tests administered by a technician: for example, the analogous test for the Timed 25-Foot Walk is the Walking Speed Test on the iPad, the 9-Hole Peg Test is called the Manual Dexterity Test, the Sloan Low Contrast Visual Acuity Test translates to the Low Contrast Visual Acuity, and the Symbol Digit Modalities Test to the Processing Speed Test.
The iPad is attached to a belt clip worn by the patient. A specially engineered device that sits on top of the iPad and is connected to it collects the relevant data, said Dr. Rudick.
He and his team performed a validation study that included 51 patients with MS and 49 healthy controls. Over and over, they found that the 2 methods were similar. For example, the test-retest reliability for various dimensions, including the T25FW and the 9 HPT, was "very good," said Dr. Rudick. "The correlations were mostly above .9, showing that it's highly reliable whether the technician does it or the iPad does it."
As for sensitivity to MS with tests of manual dexterity, visual acuity, and other tests, again, "what you see is that all of these tests, whether the technician or the iPad does them, distinguish MS patients from healthy controls," said Dr. Rudick.
Results were "very similar" for progressive versus relapsing types of MS, he added.
In some instances, the device was superior to a human tester. For example, with respect to how well a test distinguishes MS from healthy control, "for virtually every case, except the visual test, the iPad actually does a little bit better than the technician," said Dr. Rudick.
As for how well iPad or the technician measurements correlated with patient reports, that seemed to depend on the dimension. There was some correlation with certain lower-extremity patient reports, but not some upper-limb reports.
Dr. Rudick noted that the processing speed test correlated with just about everything except cognition. "MS patients don't recognise their cognitive dysfunction as a symptom they would call a cognitive problem," he explained. He added that the literature shows that cognition correlates better with depression than actual cognitive performance.
Easy to Use
The technology was well accepted. Patients found the applications were easy to understand and to use. "They said that completing the test on the iPad using a touch screen was easy, and they didn't have difficulty wearing the iPad for balance and walking," said Dr. Rudick.
Patients with MS, however, were more likely than healthy controls to find that the testing caused fatigue. "The way I interpret this is that it just reflects that patients have fatigue and can only tolerate so much testing," said Dr. Rudick.
The technology has several implications. The data can be transferred wirelessly to the "cloud" and scored instantly, enabling automatic entry into research and clinical databases. "You could theoretically send this right to the doctor at the time of the testing so he or she can see it, and at the same time send it to a research database," said Dr. Rudick.
This should reduce errors because there's no transcription of data, he added. "Whenever a human transcribes data there will be some error rates" which are estimated at about 1% or 2%.
The iPad data collection could lower costs of testing, too, because it lessens the need for extensive quality control of data and for human input. "If this can be transformed into a completely self-administered test, which we're working on right now, you don't need the technician," said Dr. Rudick.
"Nobody has the money for a technician to test their patients in practice," Dr. Rudick added in an interview with Medscape Medical News. "Also, a single technician can test a single patient, one at a time; with the iPad, several patients could test themselves simultaneously."
The technology could be adapted for "nontraditional" settings, such as rural areas, said Dr. Rudick. Because data could be collected at home, collection could be done more often, allowing for "trend analysis" over time, he said. Another implication, he noted, is that it allows researchers to develop a patient "profile" to determine how a patient is doing relative to healthy matched controls. "You can immediately grasp what is going on with patients over time." The technology also allows for input of additional tests the clinician might find useful, said Dr. Rudick.
The advantage of this technology, Dr. Rudick told Medscape Medical News, is that "walking speed, manual dexterity, vision function, and cognitive function information can be available to the neurologist." This, he said, "would allow the neurologist to track his or her patient over time, monitor the impact of medication, and make data-driven treatment decisions after discussion with the patient."
The technology still needs some tweaking. "We have to solve issues such as data transfer and integration with medical records, and we have to start building some databases from this," said Dr. Rudick. He said he hopes the technology will be available for widespread dissemination in about a year.
Work to Be Done
Asked for a comment, Robert P. Lisak, MD, professor and chair, Department of Neurology, Wayne State University School of Medicine, Detroit, Michigan, and the new president of CMSC, said the study is very interesting and promising.
"It's nice to see modern electronics and computer technology applied to the practice of medicine in a useful manner that has the potential to enhance care and cut costs but not cut costs by reducing the amount and quality of care," Dr. Lisak told Medscape Medical News.
However, he added that "there is still some work to be done on some of the measures, and we need to see if this approach can be confirmed and validated at other centers."
The validation study was supported by Novartis Pharmaceuticals. Dr. Rudick is an employee of Biogen Idec. Dr. Lisak has disclosed no relevant financial relationships.
6th Cooperative Meeting of the Consortium of Multiple Sclerosis Centers (CMSC) and the Americas Committee for Treatment and Research In Multiple Sclerosis (ACTRIMS). Symposium: iTechnology in MS: Transformation or Chaos? Presented May 29, 2014.
Source: Medscape Multispeciality Copyright © 1994-2014 by WebMD LLC (17/06/14)
Unique solutions for MS gait problems(03/06/14)
With impaired walking ability generally considered the number one functional problem for multiple sclerosis (MS) patients, new approaches to assistive devices were described here, ranging from the mechanical to the furry.
In the former category, PhD student Morgan Boes and colleagues at the University of Illinois in Urbana-Champaign (UIUC) have designed a self-contained, pneumatic-powered ankle-foot orthosis (AFO) aimed at boosting a patient's ability to push off while walking or climbing stairs.
In the latter category is Bamse, a 6-year-old boxer dog trained by Cecilie Fjeldstad, PhD, of the Oklahoma Medical Research Foundation in Oklahoma City, to provide both physical and psychological support to moderately disabled MS patients as they walk.
Both researchers described their progress to date with their respective approaches at the joint meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis (CMSC-ACTRIMS).
Pneumatic Powered AFO
Boes, who is completing her doctoral studies in the UIUC lab of Robert Motl, PhD, showed her device's design at two CMSC-ACTRIMS poster sessions.
It's powered by bottled CO2 gas worn on a belt, which is connected to an AFO that includes positional and force sensors and a pneumatic actuator that flexes the foot while increasing joint stability and motion control.
The primary goal, Boes explained, is to provide "directional powered assistance during each phase of the gait."
Passive AFOs are already widely available to support the foot and ankle in MS patients and others with weakened lower-extremity muscle function. A common problem in MS is drop foot -- impairment in the strength of ankle-foot flexion, depriving patients of the power needed to move forward while walking.
These devices stabilize the joint and hold the foot in a neutral position, which helps patients with drop foot to walk but cannot provide an actual strength boost.
The UIUC device provides up to 100 lbs per square inch (PSI) of force during three of the four gait stages: initial contact when the foot strikes the ground (stage 1), forward propulsion (stage 3), and leg advancement (stage 4). No power is delivered at the second stage, known as loading response, when the weakened foot is flat on the ground and the walker has not yet begun to push off on it.
Pilot studies with healthy people in the lab have indicated that it should perform more or less as desired, but testing in MS patients has not yet begun. Boes's group is gearing up for a trial with planned enrollment of about 30 patients already using an AFO or for whom it has been recommended. The trial will use the 6-minute walk test as the primary endpoint.
Boes admitted that the prototype's design was somewhat awkward looking (although when this was suggested to her, she laughed and said it was "sleek" relative to an earlier model). But she pointed out that it was constructed from readily available and inexpensive components and the pneumatic system was known to be both robust and safe. She said her group had considered an electromechanical design and decided it would have more minuses than pluses.
Service Dog for Walking Assistance
Fjeldstad reported on an initial trial with Bamse (Norwegian for "stuffed teddy bear," she explained, pronouncing it as "bom-suh") in 36 patients with pronounced walking impairment but who did not currently require an assistive device such as a cane or walker.
She personally trained the animal (already a certified therapy dog) to walk beside a person without pulling ahead or lagging behind, and designed a special harness with a flexible handle. Hence, the patient cannot and should not lean on the dog like a cane.
The intent is similar to that of a guide dog for the blind, Fjeldstad indicated. The person may gain some physical steadying from having a hand on the dog's harness, but the support is primarily psychological in giving the patient more confidence in walking.
In the trial, the 36 patients underwent a total of four timed 25-foot walk (T25W) tests with Bamse -- an unassisted walk followed 3 minutes later with a second walk with Bamse. After a 15-minute rest, each patient then repeated the two T25W tests but in reverse order (assisted followed by unassisted).
The mean unassisted time to complete the 25-foot walks was 9.3 seconds (SD 0.4), well in excess of the 8-second threshold for substantial impairment proposed in a Neurology paper last year by several researchers including Motl.
Bamse's assistance improved the T25W times only a little -- to a mean of 8.7 second (SD 0.3), which was statistically significant at P=0.014 -- but then, the participants had not trained with the dog before and one might expect that the confidence boost would increase with practice.
Fjeldstad said that these results should encourage more research into the use of service animals as an aid to ambulation in MS patients.
The study by Boes' group was supported by the CMSC Foundation and the National Science Foundation Research Center for Compact and Efficient Fluid Power.
The study by Fjeldstad's group had no external funding.
Authors of both studies declared they had no relevant financial interests.
Primary source: CMSC-ACTRIMS
Source reference: Boes M, et al. "Evaluation of a portable powered ankle-foot orthosis on gait function in persons with multiple sclerosis" CMSC-ACTRIMS 2014.
Additional source: CMSC-ACTRIMS
Source reference:Fjeldstad C, et al. "Does using a service dog help ambulation in MS individuals with gait dysfunction?" CMSC-ACTRIMS 2014; Abstract RH07.
Source: MedPage Today © 2014 MedPage Today, LLC (03/06/14)
A multicenter research team led by Cedars-Sinai neurologist Nancy Sicotte, MD, an expert in multiple sclerosis and state-of-the-art imaging techniques, used a new, automated technique to identify shrinkage of a mood-regulating brain structure in a large sample of women with MS who also have a certain type of depression.
In the study, women with MS and symptoms of “depressive affect” – such as depressed mood and loss of interest – were found to have reduced size of the right hippocampus. The left hippocampus remained unchanged, and other types of depression – such as vegetative depression, which can bring about extreme fatigue – did not correlate with hippocampal size reduction, according to an article featured on the cover of the January 2014 issue of Human Brain Mapping.
The research supports earlier studies suggesting that the hippocampus may contribute to the high frequency of depression in multiple sclerosis. It also shows that a computerized imaging technique called automated surface mesh modeling can readily detect thickness changes in subregions of the hippocampus. This previously required a labour-intensive manual analysis of MRI images.
Sicotte, the article’s senior author, and others have previously found evidence of tissue loss in the hippocampus, but the changes could only be documented in manual tracings of a series of special high-resolution MRI images. The new approach can use more easily obtainable MRI scans and it automates the brain mapping process.
“Patients with medical disorders – and especially those with inflammatory diseases such as MS – often suffer from depression, which can cause fatigue. But not all fatigue is caused by depression. We believe that while fatigue and depression often co-occur in patients with MS, they may be brought about by different biological mechanisms. Our studies are designed to help us better understand how MS-related depression differs from other types, improve diagnostic imaging systems to make them more widely available and efficient, and create better, more individualized treatments for our patients,” said Sicotte, director of Cedars-Sinai’s Multiple Sclerosis Program and the Neurology Residency Program. She received a $506,000 grant from the National Multiple Sclerosis Society last year to continue this research.
Also participating in the study were researchers from University Hospital, Hamburg, Germany; the University of Arizona, Tucson; David Geffen School of Medicine at UCLA; the University of California, San Francisco; Yale School of Medicine, New Haven, Conn.; and Feinberg School of Medicine at Northwestern University, Chicago.
The study was funded by the National Institutes of Health (NIH R01 MH59708, R01-HD043323, K01EB013633); Cousins Center for Psychoneuroimmunology and the National Institute on Aging (K01 AG028404); Marie Curie grant from the European Union (MC FP7-PEOPLE-2010-RG268381); Skirball Foundation; and Department of Defense (W81XWH-10-1-0882).
Citation: Human Brain Mapping, “Detection of Altered Hippocampal Morphology in Multiple Sclerosis-Associated Depression Using Automated Surface Mesh Modeling.” Cover of the January 2014 print edition.
Source: Newswise ©2014 Newswise, Inc (31/01/14)
St. Lawrence University professors and recent graduates have discovered a type of nanoparticle that may alleviate symptoms of multiple sclerosis.
Karin Heckman, assistant professor of biology, and William E. DeCoteau, associate professor of psychology, were lead authors on a research paper, published in a scientific journal, that examined cerium oxide nanoparticles and their ability to alleviate the symptoms of multiple sclerosis.
The article, titled “Custom Cerium Oxide Nanoparticles Protect Against a Free Radical Mediated Autoimmune Degenerative Disease in the Brain,” was published this month in ACS Nano, a publication of the American Chemical Society.
Ana Y. Estevez, associate professor of biology and psychology, and Joseph S. Erlichman, professor and R. Sheldon ’68 and Virginia H. Johnson Chair of Science and co-chair of the Department of Biology, were also listed as authors in the publication.
The study concluded that cerium oxide nanoparticles are widely used as catalysts in industrial applications and are considered potent antioxidants due to their free radical-scavenging properties.
Heckman, DeCoteau, and the other author’s laboratory experiments indicate the particular set of particles located in research at St. Lawrence University have the potential to alleviate the symptoms of multiple sclerosis, a neurodegenerative disease, while not causing damage to the liver and spleen of mice.
“St. Lawrence has a unique set of cerium oxide particles,” said Heckman, who specializes in infections and autoimmune diseases. “These particles move into the brain to help to provide therapy. Yet, these particles also diminish over time.”
Heckman also recently attended a Sustainable Nanotechnology Organization conference earlier this month in Santa Barbara, Calif., where she delivered a presentation titled “Differences in the Neuroprotective Effects of Nanoceria in a Murine Model of Multiple Sclerosis,” and tested St. Lawrence’s particle research against other commercially available products.
The presentation mirrored the recently published paper.
Heckman was joined at the conference by Associate Professor of Chemistry Matthew C. Skeels, DeCoteau and Erlichman.
Heckman said ultimately the development of a pharmaceutical drug is the goal.
“The question we’re asking now is how can these particles be used therapeutically if they’re packaged in the correct chemical form,” she said. “It can take up to 10 years for a drug to be fully developed, from the initial research to FDA (U.S. Food and Drug Administration) approval. But, yes, that’s the goal.”
According to Heckman, former St. Lawrence University students were instrumental in the study, monitoring experiments twice a day and conducting a series of motor tests on laboratory mice.
Source: North Country Now ©North Country 2013 (09/12/13)
As people step outdoors into the bright sunshine, their pupils automatically contract. Australian scientists are making use of how this "pupil reflex" is connected to the brain as a potential new way of testing the severity of multiple sclerosis (MS).
Scientists from the Australian Center of Excellence in Vision Science (ACEVS) based at the Australian National University (ANU) have used an instrument they are developing to accurately measure the pupil responses of MS patients and have found that the pupils of MS patients respond appreciably slower, the ANU said in a press release on Thursday.
The finding opens the door to a simple and quick way of tracking the severity of MS over time: the slower the response, the worse the MS.
"Our instrument uses special patterns of flashing lights that the patient looks at for four minutes," said Professor Ted Maddess, a vision scientist at ANU who is head of the ACEVS team.
"We use infrared cameras to measure light-induced changes in the diameters of both pupils, and with computer tracking we can measure the diameter to within a micrometer 30 times a second," he said.
"We have just published the results of our study of 85 MS patients, and we find that in MS patients the pupil response is about 25 milliseconds slower than in our control group. Although the study is preliminary, we believe the test has good potential in individual patients because it can precisely measure the speed of their response to within a millisecond."
Maddess said instead of an expensive MRI to track the condition, the new method gives an accurate readout after just a few minutes. That quick and easy test might, in the future, allow MS patients to be assessed on the spot and have their medication adjusted accordingly.
Source: Global Post Copyright 2013 GlobalPost (05/12/13)