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)
Intrathecal baclofen in MS and spinal cord injury: complications and long-term dosage evolution(08/08/13)
Objective:To investigate the long-term dosage evolution and complication rate of intrathecal baclofen use in multiple sclerosis and spinal cord injury patients, based on a large population with a long follow-up.Design:Retrospective data analysisSetting:Academic hospital
Subjects:Patients with multiple sclerosis (n = 81) or spinal cord injury (n = 49) having an intrathecal baclofen pump implanted at the University Hospitals Leuven between 1988 and 2009.
Intervention:Medical records review of included patients in August 2010.
Main measures:Complications linked to intrathecal baclofen therapy. Daily baclofen dosage after 3 and 6 months, and yearly thereafter. Data on dosage evolution were analysed using a mixed-effect linear model.
Results:In 130 patients with a mean follow-up of 63 months, comprising 797 pump years, 104 complications were recorded. This corresponds to a complication rate of 0.011 per month, equally divided among both groups. Seventy-eight of these complications were catheter related. The mean dosage of baclofen stabilizes two years after implantation at 323 µg/day in the multiple sclerosis population. In spinal cord injury patients the daily dose only stabilizes after five years at a significantly higher dosage (504 µg/day). No significant increase in dosage is seen in the long term.
Conclusions:In multiple sclerosis and spinal cord injury patients, intrathecal baclofen therapy has a complication rate of 1% per month. Complications are mainly due to catheter-related problems (74%). The intrathecal baclofen dosage stabilizes in the long term, indicating that long-term tolerance, defined as progressive diminution of the susceptibility to the effects of a drug, is not present.
Draulans N, Vermeersch K, Degraeuwe B, Meurrens T, Peers K, Nuttin B, Kiekens C.
Department of Physical Medicine and Rehabilitation, University Hospitals Leuven, Belgium.
Source: Clin Rehabil. 2013 Jul 15 & Pubmed PMID: 23858524 (08/08/13)
Researchers at the University of British Columbia have developed a new magnetic resonance imaging (MRI) technique that detects the telltale signs of multiple sclerosis in finer detail than ever before – providing a more powerful tool for evaluating new treatments.
The technique analyzes the frequency of electro-magnetic waves collected by an MRI scanner, instead of the size of those waves. Although analyzing the number of waves per second had long been considered a more sensitive way of detecting changes in tissue structure, the math needed to create usable images had proved daunting.
Multiple sclerosis (MS) occurs when a person’s immune cells attack the protective insulation, known as myelin, that surrounds nerve fibres. The breakdown of myelin impedes the electrical signals transmitted between neurons, leading to a range of symptoms, including numbness or weakness, vision loss, tremors, dizziness and fatigue.
Alexander Rauscher, an assistant professor of radiology, and graduate student Vanessa Wiggermann in the UBC MRI Research Centre, analyzed the frequency of MRI brain scans. With Dr. Anthony Traboulsee, an associate professor of neurology and director of the UBC Hospital MS Clinic, they applied their method to 20 MS patients, who were scanned once a month for six months using both conventional MRI and the new frequency-based method.
Once scars in the myelin, known as lesions, appeared in conventional MRI scans, Rauscher and his colleagues went back to earlier frequency-based images of those patients. Looking in the precise areas of those lesions, they found frequency changes – indicating tissue damage – at least two months before any sign of damage appeared on conventional scans. The results were published in the June 12 issue of Neurology.
“This technique teases out the subtle differences in the development of MS lesions over time,” Rauscher says. “Because this technique is more sensitive to those changes, researchers could use much smaller studies to determine whether a treatment – such as a new drug – is slowing or even stopping the myelin breakdown.”
Source: University of British Columbia © UBC 2013 (13/06/13)
Decisions to change multiple sclerosis treatments soon after starting them appear to be driven more by MRI findings of increasing disease activity than worsened clinical symptoms, a researcher said here.
In a retrospective analysis of 606 patients showing suboptimal responses to an initial disease-modifying therapy, the factor showing the strongest association with a change in treatment was increased disease activity seen in MRI scans (odds ratio 6.3 compared with a single relapse alone, 95% CI 3.1-12.9), reported Barbara Teter, PhD, MPH, of the State University of New York at Buffalo.
Oddly, though, the patients least likely to change treatments were those showing relapses plus either worsened disability or increased MRI lesions, according to Teter. She and her colleagues had no firm explanation for this finding, but their hypothesis is that such patients are psychologically resistant to seeking other treatments, she told MedPage Today.
Other factors associated with increased or decreased likelihood of changing treatments after a suboptimal initial response included multiple relapses, disability progression, patient age, and time elapsed from diagnosis to initiation of disease-modifying treatment.
Teter and colleagues reviewed data from 1,448 patients in a New York state registry of MS patients from 1996 to 2009, comprising 14 MS clinics and neurology practices. Records were complete for 606 patients who had started treatment with either interferon-beta (Rebif, Avonex, Betaseron) or glatiramer acetate (Copaxone) and subsequently suffered an MS "event."
An event was defined as a clinical relapse, disability worsening as measured on the Expanded Disability Status Score (EDSS) system, increases in MRI lesion volumes or counts, or any combination of these noted at a single clinic visit. Patients who changed treatments after a second MS event separated in time from the first were not included in the analysis.
Patient demographics and clinical characteristics were reflective of the general MS population starting on disease-modifying drugs during the study period. About 75% were women, they were in their early 30s on average at symptom onset, and they started their first disease-modifying treatment a mean of about 8 years later. Mean EDSS score at initiation of disease-modifying therapy was 2.3 (SD 1.6).
Of the 606 patients in the analysis, 214 changed to another disease-modifying treatment within 6 months of an event, whereas the other 392 remained on their initial therapy. Switchers changed treatments a mean of 3.4 years (SD 2.7) after starting the first therapy.
The most common event in the overall sample was EDSS worsening alone, seen in 25% of patients, followed by relapse alone (22%), MRI worsening alone (16%), and relapse combined with EDSS worsening (16%). Other combinations were seen in less than 10% of patients.
Among those switching treatments, 32% did so after experiencing MRI worsening alone, compared with 8% of those not switching. Another 32% of switches occurred after EDSS worsening alone, whereas that was the index event in 21% of non-switchers.
In a logistic regression adjusted for clinical and demographic characteristics and clinic location, Teter and colleagues calculated the following odds ratios for switching after a given type of event, with a single relapse alone as the reference:
MRI worsening alone: OR 6.3 (95% CI 3.1-12.9)
EDSS worsening alone: OR 2.2 (95% CI 1.2-4.1)
MRI and EDSS worsening combined: OR 2.5 (95% CI 1.1-5.9)
Multiple relapses plus MRI and/or EDSS worsening: OR 0.62 (95% CI 0.24-1.60)
Such factors as time from EDSS worsening to initiating the first disease-modifying treatment or the time from starting treatment to the first event were not related to the likelihood of switching, the researchers found.
But older age was negatively associated with likelihood of switching (OR 0.46, 95% CI 0.30-0.71). Clinic location was also a significant factor, suggesting that switching may be discouraged or encouraged in specific practices.
In explaining the strong apparent effect of MRI results on treatment decisions, Teter told MedPage Today that these findings may weigh especially heavily on clinicians' judgment. When MRI scans show increased disease activity, that may drive many clinicians to recommend a different therapy, she said -- more so than findings of relapse alone.
But she pointed out that the study period of 1996 to 2009 was a significant limitation to the analysis. At that time, the interferons, glatiramer acetate, and natalizumab (Tysabri) were the only disease-modifying therapies available. Moreover, Teter said, the study spanned the interval in 2005 and 2006 when natalizumab was taken off the U.S. market, leaving even fewer options.
Since then, a series of oral disease-modifying treatments have been approved including fingolimod (Gilenya), teriflunomide (Aubagio), and dimethyl fumarate (Tecfidera, BG-12), availability of which may alter patients' and clinicians' decision-making when responses to first-line drugs are suboptimal. Teter said her group plans to update the analysis with more current data.
The study was supported by Novartis. Two co-authors were Novartis employees.
Teter reported relationships with Novartis, Biogen Idec, Teva, Avanir, and EMD-Serono.
Primary source: CMSC-ACTRIMS Joint Meeting
Source reference: Teter B, et al "Predictors of switching first-line disease-modifying therapy for MS patient" CMSC-ACTRIMS 2013; Abstract DX56.
Source: MedPage Today © 2013 MedPage Today, LLC. (03/06/13)
Smartphone apps to store your grocery list, find your car, and remind you to take your medication can help combat memory loss caused by multiple sclerosis.
Multiple sclerosis (MS) patients often struggle to keep track of doctor's appointments, children's school trips, and other elements of a busy, 21st-century schedule. But a new slate of digital tools can help patients with this neurological condition control the chaos and keep helpful reminders at their fingertips.
According to MS specialist Dr. Daniel Kantor, "One of the toughest symptoms for people with MS, their loved ones, and their neurologists, is memory loss. This can range from difficulty with multi-tasking and the tip-of-the-tongue phenomenon ('what’s that word I’m looking for?') to difficulty with remembering important life events."
When measuring and treating memory loss, one size doesn't necessarily fit all.
"Your neurologist may do the memory testing themselves or they may send you to a neuropsychologist...who specializes in doing hours of memory testing to help your neurologist better characterize what types of memory problems you are having [and] best figure out what part of the brain is involved," Kantor said in an interview with Healthline. "Some people do well with visual hints, and a neuropsychologist can help with making suggestions, such as using Post-It notes and reminders."
Now, with the addition of a few select applications, or “apps”, MS sufferers can quickly type—or even speak—these reminders into their cell phones.
Timely Reminders Could Save Your Life
There's no substitute for preparedness, and patients with MS know the unpredictable nature of their disease. Even those who do not suffer from memory loss can panic and forget critical information during a crisis.
In Case of Emergency, or ICE, is an app that can be used to store vital data about a patient's condition, allergies, medications and emergency contacts on his or her mobile device. First responders are trained to look for these emergency apps. Having this information organized in one place, where EMTs can easily retrieve it, can shave critical minutes off time otherwise spent sorting through a purse or a wallet—time that could be spent saving a life.
Memory loss can also impact the daily routine of taking medications. A majority of MS patients are prescribed one of a slate of disease-modifying drugs. Remembering to take their pill or perform their injection each day is necessary to ensure the efficacy of the treatment.
MediSafe, a virtual pillbox app released in November 2012, not only reminds you to take your meds, but also syncs data with your family members' devices, alerting them to missed medications so they can provide a gentle reminder as well.
“Medication adherence is a persistent and elusive problem, interrupting patients’ wellbeing, costing health providers and insurers billions annually, and causing preventable deaths,” said MediSafe Project CEO Omri ‘Bob’ Shor in a press release. “MediSafe Project’s involvement of patients’ loved ones and caretakers is proving itself a breakthrough in reducing the harm that comes from medication non-adherence.”
MediSafe reports that after eight weeks, 81 percent of its users were taking their medications on time. That’s a 31 percent jump from the World Health Organization’s estimated average medication adherence rate of only 50 percent.
Memory loss impacts other aspects of an MS sufferer’s life as well. Simply remembering their parking spot at the mall can be a daunting task.
MyCar Locator, released in December 2011, utilizes your cell phone's GPS to set coordinates when you press the “park” button. When you want to return to your car, the app will lead you back to your vehicle with a simple directional arrow and approximate distance.
Out of Milk is another daily routine essential. The app allows users to create, sort, and share shopping and to-do lists, and also displays coupons and promotions from local grocery stores.
"We have been contacted by grateful users suffering from a range of issues including cognitive memory loss, patients suffering through chemotherapy, multiple sclerosis, and more who all tell us the same thing: Out of Milk has helped them and their families manage their shopping lists and save money quickly and easily," said Paul Sheaffer, co-founder of Capigami and developer of Out of Milk in an interview with Healthline.
"One of the core features of Out of Milk is it's ability to share lists in real-time," Sheaffer added. "We've found that many users going through medical hardship use this feature to share their needs with friends or family who also use the app who can then do their shopping for them."
The apps above are all available through the Google Play store for Android phones, but there are thousands more apps in the Amazon Appstore and on iTunes to help patients take charge of their daily and long-term goals.
"We think of our memory and the way we think as what makes us uniquely human," Kantor said. "Feeling like you are not thinking as well as you used to can make you feel like you have lost something. Some people feel depressed when they've lost a piece of themselves and that's why it is so important to alert the people around you about how you are feeling and not let yourself fall into depression, Remember, you are not alone!"
Source: Healthline Copyright © 2005 - 2013 Healthline Networks, Inc (14/05/13)
Spinal cord lesions imaged with quantitative MRI-based technologies correlated significantly better with clinical disability of multiple sclerosis (MS) patients than did simple lesion counts based on conventional MRI, researchers said.
Irrespective of whether patients had high or low lesion counts on conventional MRI scans, those with greater levels of abnormality in quantitative MRI measures such as diffusivity and anisotropy were significantly more likely to show high levels of clinical disability (P<0.05), according to Jiwon Oh, MD, of Johns Hopkins University, and colleagues.
The strong correlation stood in contrast to the near-total lack of association between simple lesion counts and clinical disability historically seen in MS patients, the researchers contended in their report in the Feb. 5 issue of Neurology.
"These findings support the concept that microstructural changes undetectable by conventional lesion count contribute substantially to clinical disability in MS, and suggest that quantitative MRI measures have the ability to provide clinically relevant information beyond that which may be gleaned from measures of MRI lesion load alone," Oh and colleagues wrote.
Currently, MRI studies in MS patients focus on the number of lesions and their volume, which can be discerned from standard scans.
But ever since the introduction of these scans as a tool for evaluating MS disease activity, clinicians have noted "the clinicoradiological paradox," as Oh and colleagues put it, in which patients with high lesion counts may not show marked clinical symptoms. Moreover, substantial clinical disability may occur in patients with relatively few lesions.
Noting that newer MRI technology -- including diffusion tensor and magnetization transfer imaging -- allows more detailed, quantitative measurement of lesions, Oh and colleagues sought to evaluate whether additional parameters would correlate more closely with disability.
They studied 124 MS patients, about two-thirds of whom were female, with a mean disease duration of 11 years (SD 9). Their median score on the Expanded Disability Status Scale (EDSS) was 3.5, but the range was substantial enough for the researchers to divide them into "low" and "high" disability groups (median EDSS score 2.5 and 6.5, respectively).
Patients were also stratified into high and low lesion counts (mean 3.6 and 1.2, respectively), such that there were a total of four groups: low lesion with low disability, low lesion with high disability, and so on.
MRI scans of the cervical spine were taken and processed with diffusion tensor and magnetization transfer analyses.
In addition to conventional counts of lesions, these analyses provided measures of five other parameters:
Magnetization transfer ratio
Mean lesion counts were not significantly associated with EDSS scores in the sample. But most of the five additional MRI parameters measured were significantly different in the high- versus low-disability groups, irrespective of whether lesion counts were high or low.
In the low-lesion patients, the three diffusivity parameters were significantly higher (P<0.03) with high versus low disability. The magnetization ratio was significantly lower with high disability (P=0.003), as was fractional anisotropy (P=0.03).
The same pattern was seen in the patients with high lesion counts, except that the differences between high- and low-disability patients did not reach statistical significance.
Oh and colleagues noted that the EDSS scale is itself an imperfect measure of disability, insofar as it emphasizes walking ability over other functional outcomes such as manual dexterity or bladder continence.
Other limitations to the study included the researchers' choice of cutoffs for high versus low disability and lesion counts, certain difficulties they faced in obtaining the spinal cord MRI scans, and their decision not to include lesion volume in their analyses.
The study was funded by the Multiple Sclerosis Society of Canada, the National Multiple Sclerosis Society, and the National Institute of Neurological Disorders and Stroke.
Study authors reported relationships with Teva, MedicalLogix, Diagnosoft, Philips Healthcare, Novartis, Biogen Idec, Versex, Vaccinex, EMD Serono, Bayer, and Abbott.
Primary source: Neurology
Source reference: Oh J, et al "Spinal cord quantitative MRI discriminates between disability levels in multiple sclerosis" Neurology 2013; 80: 540-547.
Source: MedPage Today © 2013 MedPage Today, LLC (03/02/13)
A simple, non-invasive eye test could offer a way to measure how fast multiple sclerosis is progressing in a patient. The scan, known as Optical Coherence Tomography (OCT), takes just a few minutes per eye and can be performed at a GPs surgery.
Researchers from John Hopkins University performed scans on 164 M.S. patients, measuring the thickness of the lining at the back of the eye. It was determined that patients with thinning of the retina had both earlier and more active forms of the disease.
Fifty-nine of the patients showed no symptoms. All patients received exams for six months for around 21 months. They also gave them MRI brain scans once a year.
Multiple sclerosis is a disease that affects nerves in the brain and spinal cord, causing problems with muscle movement, balance and vision.
Around eight out of 10 people with M.S. have a type known as relapsing remitting. People will have periods where symptoms are mild or disappear altogether followed by flare-ups with this version of the disease. After around 10 years, half of patients will develop secondary progressive disease where symptoms get worse, with little remission.
Monitoring the disease is highly difficult because its course can be unpredictable. Scientists believe OCT could provide a good way to do this.
"As more therapies are developed to slow the progression of MS, testing retinal thinning in the eyes may be helpful in evaluating how effective those therapies are," study author Dr Peter Calabresi says.
The study found that people with MS relapses had 42 percent faster thinning than people with MS who had no relapses.
In addition, the MRI scans revealed people with MS who had signs of active inflammation, such as gadolinium-enhancing lesions experienced 54 percent faster thinning.
Patients, in the meantime whose level of disability worsened during the study experienced 37 percent more thinning than those who had no changes in their level of disability.
The study was supported by the National Multiple Sclerosis Society, the National Eye Institute and Braxton Debbie Angela Dillon and Skip Donor Advisor Fund.
Source: Catholic Online Copyright 2012 Catholic Online (27/12/12)
Transparency Life Sciences picked up a win for its bet on open innovation in transforming drug development. The FDA cleared the developer's IND application to study a generic hypertension drug for a new potential use in patients with multiple sclerosis, after the startup tapped crowdsourced input from experts and patients on aspects of the clinical trial.
The study not only used New York-based Transparency's web-based Protocol Builder software to gather ideas on the design of the Phase II effort, but the trial will also be partially virtual. After patients' initial visits to trial sites, the planned 12-month study is expected to use telemonitoring technology from Advanced Monitored Caregiving and other partners to track participants until their final checkups, COO Marc Foster explained to FierceBiotechIT.
With these outside-the-box strategies, Transparency aims to drive down the cost of clinical trials by at least 50%. This is a big goal and one not easily achieved industry-wide, and at first blush, the startup's bold idea might draw some healthy skepticism. As published in a Nature Reviews Drug Discovery article in March, the number of FDA approvals per billion dollars in research money spent has been steadily declining over the past 60 years or so. The authors dubbed this "Eroom's Law," which is Moore's Law spelled backwards. Transparency's Foster believes there is hope for reversing the troubling trend.
"I think it's doable. It takes a fresh approach. It takes a bold approach," Foster said in a phone interview. "Just tinkering with the status quo is not working, and it's really resulted in an unsustainable clinical development model that has translated into escalating costs."
How does Transparency expect to drastically reduce the cost of clinical research? For starters, the company is crowdsourcing patients and healthcare experts to augment its reliance on internal thought leaders to design trial protocols. Its hope is to show that this is an efficient and effective approach to protocol design, which can take substantial time and money to complete.
In the MS study, the company wants to trial a new use of a widely prescribed generic heart drug in the ACE inhibitor lisinopril, which has a well-established safety profile that allows the startup to begin its program with a midstage study. (A company co-founder documented the generic drug's benefits for MS in animal studies, resulting in a new method of use patent filing.) Foster also aims to get discounted supplies of the drug from generics companies. Overall, he sees an opportunity to pick up drugs that are ready for Phase II from around the industry, using the company's open innovation approach to reduce development costs of the molecules, with plans to license successful candidates to partners after midstage studies. The partners would foot the hefty bills for Phase III trials.
The company has found a lead investigator at Stanford who treats many MS patients, and Foster sees an opportunity to cut recruitment costs by enrolling all the estimated 150 to 180 study participants from the San Francisco Bay Area. Recruitment is notoriously expensive, and drawing from the investigator's large pool of patients for the study could significantly reduce that expense.
The next bucket of savings is expected to come from reduced clinical monitoring costs because participants will self-report their status from their homes with mobile devices for most of the study, reducing the cost of traveling to clinics with high costs of doing business, Foster says. Transparency is considering a GPS-enabled system to provide remote monitoring of MS patients' movements, as their neurological disorder causes progressive disability.
Transparency is taking a hybrid approach to virtual clinical development that might just work. We'll keep track of its progress.
Source: FierceBiotechIT © 2012 FierceMarkets (20/12/12)
Researchers say they've been able to use nanoparticles to stop multiple sclerosis (MS) in mice that are bred to have the disease.
The particles are about 200 times smaller than the thickness of a human hair. They are made from the same material that's used to create dissolving stitches.
When researchers attach specific proteins to the particles, they say they're able to teach the body not to attack its own tissues.
If the approach succeeds in human studies, it may one day lead to more targeted treatments not only for multiple sclerosis but also for other kinds of autoimmune disorders, including type 1 diabetes and rheumatoid arthritis.
The research is published in the journal Nature Biotechnology. The study was funded by grants from the National Institutes of Health, the Myelin Repair Foundation, the Juvenile Diabetes Foundation, and the Australian government.
Turning Down an Autoimmune Attack
In multiple sclerosis, the body attacks its own myelin. Like the insulation around electric wires, myelin is a material that coats nerve fibers, allowing them to effectively carry signals that power the body.
Over time, people with MS may develop a host of problems related to myelin damage, including trouble with muscle coordination, movement, numbness, pain, and vision problems. About 80% of people with MS have the relapsing-remitting form. The mice in this study were bred to have this type of MS.
Researchers wondered if they could stop that process by making use of the body's "garbage disposal system." In addition to protecting the body from foreign invaders, an important role of the immune system is getting rid of dead cells.
When dead or dying cells pass through the spleen, big white blood cells called macrophages gobble them up. As part of this process the macrophages send signals to other parts of the immune system, letting them know that the dying cells aren't dangerous, just routine bits of trash that need to go.
Years ago, researcher Stephen D. Miller, PhD, an immunologist in the Feinberg School of Medicine at Northwestern University in Chicago, figured that it might be possible to hijack this garbage removal system and get the body to recognize -- and then ignore -- proteins it was mistaking for threats.
"What we've done is simply tap into a system that the immune system was smart enough to evolve millions of years ago to get rid of dead and dying cells," Miller says.
He's already tried the approach in humans using white blood cells that were first collected and then killed. He then attached proteins to the dying cells and infused them into the body. In an early safety trial, Miller says that approach appeared to be well tolerated.
"There [were no side effects], there was no re-triggering of disease, and we actually showed that immune responses in patients were decreased," Miller says.
But other immune responses, such as protection against certain infections, remained strong. That suggests that patients treated this way wouldn't see the kind of general immune suppression that happens with current treatments for autoimmune diseases.
The problem with using whole cells, however, is that it's time consuming and expensive.
So Miller wondered if it might be possible to try the same thing with synthetic nanoparticles. First they tried tiny plastic beads. But since those don't break down in the body, he asked his Northwestern colleague Lonnie Shea, PhD, who is a biomedical engineer, for help finding another material that might be safer.
They decided on poly(lactide-co-glycolide), or PLG. It's a material that's used to make sutures, grafts, and other things that are meant to slowly dissolve in the body. By first dissolving PLG and then spinning the watery solution very rapidly, they were able to make tiny particles that could carry myelin proteins.
When they infused these protein-coated particles into the mice, they were able to both prevent the development of a mouse disease that mimics MS and to stop attacks in mice that already had the disease.
"We think this is actually a simpler option. You don't have to manipulate cells and put an antigen on them. This way, you could have an off-the-shelf product," Shea says.
What's more, the nanoparticles can be coated in many different kinds of proteins, which means they could one day treat other kinds of autoimmune diseases and even problems like food allergies.
"There are just so many possible applications of this, it's fun to think about," says Shea.
First, though, the technology has to be tested in humans. Before that can happen, Miller says they need to conduct more animal trials. If all goes well, he thinks the first human studies might be two years away.
Source: WebMD ©2005-2012 WebMD, LLC. (19/11/12)
Further to that stated in Brainsway's periodic report for 2011 regarding the double-blind clinical trial being conducted at the Charite Hospital in Berlin and at the University Medical Center Hamburg-Eppendorf in Hamburg to assess the safety and efficacy of the Company's Deep TMS device for the treatment of fatigue and depression symptoms in multiple sclerosis (MS) patients, the Company is pleased to announce the final results of the trial.
The final results are in respect of 28 patients (out of 34 recruited into the trial originally). The trial subjects were divided into three groups: a sham-stimulation control group, a treatment group that received high-frequency (18 Hz) left prefrontal stimulation, and an additional treatment group that received low-frequency (5 Hz) motor cortex stimulation. Each subject received a series of treatments, three times a week over six weeks. The effects of the treatment were evaluated during the treatment period and over the course of the subsequent 6-week period.
The effects of the treatment on subjects' fatigue levels were assessed using standard fatigue rating scales such as the Fatigue Severity Scale (FSS), the Modified Fatigue Impact Scale (MFIS), the Epworth Sleepiness Scale (ESS) and the Visual Analogue Scale (VAS); and its effects on subjects' depression levels were assessed using the Hamilton Rating Scale for Depression, the Beck Depression Inventory (BDI) and the Positive and Negative Affect Scale (PANAS). The present study was primarily concerned with treating fatigue and depression, and did not examine the stimulation parameters for treating the motor symptoms of MS.
Measures of Device Safety
No serious side effects were reported in the study. Mild side effects were reported by some of the subjects in each group, but these resolved on their own within a few days.
Efficacy of Deep TMS Device for Treatment of Depression and Fatigue Symptoms
Measures of Fatigue - Analysis of fatigue rating scale scores revealed a statistically significant (p<0.05) improvement on all scales in the 5-Hz motor cortex stimulation treatment group, with onset of improvement on some of the scales occurring only after the conclusion of the treatment series. In contrast, the 18-Hz left prefrontal stimulation treatment group exhibited significant improvement (p<0.05) in scores only on the ESS and VAS, while the sham-stimulation control group improved significantly (p<0.05) only on the VAS.
Measures of Depression - A significant improvement on the BDI and the PANAS was observed in the 5-Hz motor cortex stimulation group (p=0.001 and p=0.046, respectively), while the other groups' scores on these depression rating scales did not change significantly.
According to the investigators, these results indicate that Deep TMS therapy with the Company's device is safe and effective for the treatment of fatigue and depression symptoms in MS patients. They also note that additional, more extensive studies should be performed to explore the effects of Deep TMS treatment.
Source: Yahoo! Finance Copyright © 2012 GlobeNewswire (16/11/12)
The connection is common. Eyes are like windows — they can reveal as much about a person as a bay casement can about the room it illuminates. And according to two studies recently released by Johns Hopkins University, that predominantly spiritual image may, now more firmly than ever, actually have a basis in scientific fact.
Johns Hopkins researchers found that an inexpensive eye scan system has the ability to assess brain inflammation accurately in people with devastating autoimmune disorders, such as multiple sclerosis (MS). The tool, known as optical coherence tomography (OCT), surveys the nerves deep in the rear of the eye, evaluating previously immeasurable layers of light-sensitive retinal tissue. What’s more, an OCT costs one-tenth of an MRI; it also doesn’t apply harmful radiation to the patient being tested.
"Eye scans are not that expensive, are really safe, and are widely used in ophthalmology, and now that we have evidence of their predictive value in MS, we think they are ready for prime time,” Peter A. Calabresi, MD, a professor of neurology at the Johns Hopkins University School of Medicine and leader of the studies, said in a news release. “We should be using this new quantitative tool to learn more about disease progression, including nerve damage and brain atrophy."
For one examination — the results of which were published in the journal Lancet Neurology — Calabresi and his team measured the swelling of the inner layer of the retina in 164 patients with MS; 60 control patients were also involved, and all of the studies’ cohort were given MRIs to measure possible swelling in the brain. If swelling was particularly severe in a given patient’s OCT scan, researchers found that the brain showed a similar increase in inflammation, suggesting a direct relationship between the organs.
In a second study Calabresi and colleagues looked at eye and brain scans of 84 MS patients and 24 healthy controls. This time, they focused on two other deep retinal layers, the ganglion cell layer + inner plexiform layer (GCL+IPL), and the peripapillary retinal nerve fiber layer (pRFNL). Greater cell wasting in those areas was strongly correlated with more atrophy in the gray matter of the brain, signifying more nerve damage from MS.
Collectively, both studies trumpeted the effectiveness of OCTs in relaying valuable information about the brain, through the eye.
“It’s a way of driving quantitative information about how healthy the nerves are in the back of the eye,” Calabresi said. “And now that it definitively relates to what’s happening in the rest of the brain, we think that certainly every MS clinic should have this and we’re starting to develop some evidence that it may have applications in other neurological diseases like Alzheimer’s disease, maybe Parkinson’s disease.”
Calabresi expressed to PhysBizTech that while some of the results were surprising, information such as this was right on point.
“The surprising part was that the patient has much inflammation in their eyes and actually had what we would call macular edema — the swelling in the back of the eye, the retina, that had previously been mostly linked with patients who have diabetes or typically if they were older patients,” he said. “It hadn’t been described in many patients who had multiple sclerosis previously, so that was a surprise. And the extent of the inflammation was a surprise. We were going into this hypothesizing that the eye was going to be a window into the brain, so the fact that it did have a predictive value for the brain parameters of MS was not totally surprising, but of course we were pleased that the results were highly significant.”
The findings suggest that more of neurology become acquainted with OCT scans as a means to further develop prognosis practices in the beginning stages of MS and other similar conditions.
“It’s really not diagnostic; it’s prognostic,” Calabresi added. “You still need other information to diagnosis the disease and the findings that we are looking at are not necessarily specific to MS, they can be seen in other disease. But I do think that they will have a role in assessing patients and determining whether they are at risk for more aggressive forms of the disease.”
Calabresi listed the following as key aspects physicians and specialist should remember about the research:
1. These little micro-cysts that are a form of macular edema can actually occur in young people with MS. If people see or hear that they have macular edema, they should start thinking beyond the eye, thinking that this could be a sign of inflammation in the rest of the brain as well.
2. MS may not be a disease that’s limited to the milinated portions of the nervous system. We think that this may really shift our thinking about MS, guide us toward thinking about MS as an inflammatory disease of the nervous system and not just the milan.
3. This [method] could be used as an outcome measure in clinical trials, reparative therapies.
Source: PhysBizTech © 2012 MedTech Media (19/10/12)
Using a high-tech imaging process to measure the thickness of the eye's retina may one day predict the progression of multiple sclerosis, a new study suggests.
The finding might lead to better ways to judge the effectiveness of treatments because different parts of the retina seem to indicate different aspects of the disease and the toll it takes on different parts of the brain, the researchers said.
The report was published online Oct. 1 in the Archives of Neurology.
Multiple sclerosis is thought to be an autoimmune disease that attacks the central nervous system, which consists of the brain, the spinal cord and optic nerves. Symptoms range from mild effects, such as numbness in the limbs, to severe, such as paralysis or blindness.
"In treating multiple sclerosis we have been tremendously successful in reducing the number of attacks," said Dr. Ari Green, assistant clinical director of the Multiple Sclerosis Center at the University of California, San Francisco, and author of an accompanying editorial in the journal.
That's the inflammatory part of the disease, Green explained. "We are very successful at treating inflammation in multiple sclerosis. We are less successful in being able to treat or reverse disability," he said.
Methods that help speed up the testing of therapies are needed if progress in treating the disability caused by MS is going to happen, Green said.
And because the retina is part of the central nervous system, it's like a window to the brain and can provide a lot of information about different areas of the brain, he explained.
"If we can figure out how to properly use this imaging [called optical coherence tomography] -- perhaps with other tests -- for predicting disability in multiple sclerosis, we could accelerate therapies that could make a difference in patients' lives," Green said.
The retina is the light-sensitive layer of tissue at the back of the inner eye. It switches images to electric signals and sends them through the optic nerve to the brain.
For the new study, the researchers looked at the retinas of 84 patients with multiple sclerosis and compared them with 24 healthy people.
"The inner and outer retinal layer thickness, measured by optical coherence tomography, may reflect global and potentially distinct central nervous system processes in multiple sclerosis," said lead researcher Dr. Shiv Saidha, a neurologist at Johns Hopkins University.
These findings may not be associated with the condition of the eye, but rather with changes in the brain itself, he said.
"If confirmed, the implications of our study findings are that OCT [optical coherence tomography] -- a relatively inexpensive, non-invasive, well-tolerated, reproducible and easily repeatable investigation -- may be a complementary technique to MRI [magnetic resonance imaging], providing useful information regarding the global aspects of the multiple sclerosis disease process," Saidha said.
The imaging technique may help researchers evaluate the effectiveness of new treatments because their impact might be reflected in changes in the retina, Saidha added.
Green said the technique might also have similar potential for other brain diseases such as Parkinson's and Alzheimer's disease.
"Everything we have tried to prevent neurodegeneration so far has failed," Green said. "We don't have any treatments in that area that are of proven benefit the way we do in heart disease and cancer. So it's a huge unmet need to treat neurodegenerative disease."
Source: US News Health © 2012 U.S.News & World Report LP (02/10/12)