(Press-News.org) SAN FRANCISCO, CA—November 27, 2012—Scientists at the Gladstone Institutes have defined for the first time a key underlying process implicated in multiple sclerosis (MS)—a disease that causes progressive and irreversible damage to nerve cells in the brain and spinal cord. This discovery offers new hope for the millions who suffer from this debilitating disease for which there is no cure.
Researchers in the laboratory of Gladstone Investigator Katerina Akassoglou, PhD, have identified in animal models precisely how a protein that seeps from the blood into the brain sets off a response that, over time, causes the nerve cell damage that is a key indicator of MS. These findings, which are reported in the latest issue of Nature Communications, lay the groundwork for much-needed therapies to treat this disease.
MS, which afflicts more than two million people worldwide, develops when the body's immune system attacks the brain. This attack damages nerve cells, leading to a host of symptoms including numbness, fatigue, difficulty walking, paralysis and loss of vision. While some drugs can delay these symptoms, they do not treat the disease's underlying cause—which researchers are only just beginning to understand.
"To successfully treat MS, we must first identify what triggers the disease and what enables its progression," said Dr. Akassoglou, who also directs the Gladstone Center for In Vivo Imaging Research and is a professor of neurology at the University of California, San Francisco, with which Gladstone is affiliated. "Here, we have shown that the leakage of blood in the brain acts as an early trigger that sets off the brain's inflammatory response—creating a neurotoxic environment that damages nerve cells."
Dr. Akassoglou and her team reached this conclusion by using advanced imaging techniques to monitor the disease's progression in the brain and spinal cord of mice modified to mimic the signs of MS. Traditional techniques only show "snapshots" of the disease's pathology. However, this analysis allows researchers to study individual cells within the living brain—and to monitor in real-time what happens to these cells as the disease worsens over time.
"In vivo imaging analysis let us observe in real-time which molecules crossed the blood-brain barrier," said Dimitrios Davalos, PhD, Gladstone staff research scientist, associate director of the imaging center and the paper's lead author. "Importantly, this analysis helped us identify the protein fibrinogen as the key culprit in MS, by demonstrating how its entry into the brain through leaky blood vessels impacted the health of individual nerve cells."
Fibrinogen, a blood protein that is involved in coagulation, is not found in the healthy brain. In vivo imaging over different stages of disease revealed, however, that a disruption in the blood-brain barrier allows blood proteins—and specifically fibrinogen—to seep into the brain. Microglia—immune cells that act as the brain's first line of defense—initiate a rapid response to fibrinogen's arrival. They release large amounts of chemically reactive molecules called 'reactive oxygen species.' This creates a toxic environment within the brain that damages nerve cells and eventually leads to the debilitating symptoms of MS.
Importantly, the team found a strategy to halt this process by genetically modifying fibrinogen in the animal models. This strategy disrupted the protein's interaction with the microglia without affecting fibrinogen's essential role as a blood coagulant. In these models, the microglia did not react to fibrinogen's arrival and did not create a toxic environment. As a result, the mice failed to show the type of progressive nerve cell damage seen in MS.
"Dr. Akassoglou's work reveals a novel target for treating MS—which might protect nerve cells and allow early intervention in the disease process," said Ursula Utz, PhD, MBA, a program director at The National Institutes of Health's National Institute of Neurological Disorders and Stroke, which provided funding for this research.
"Indeed, targeting the fibrinogen-microglia interactions to halt nerve-cell damage could be a new therapeutic strategy," said Dr. Akassoglou. "At present we are working to develop new approaches that specifically target the damaging effects of fibrinogen in the brain. We also continue to use in vivo imaging techniques to further enhance our understanding of what triggers the initiation and progression of MS. "
INFORMATION:
Jae Kyu Ryu, PhD, Mario Merlini, PhD, Kim Baeten, PhD, Natacha Le Moan, PhD, Mark Petersen, MD, Dimitri Smirnoff, Catherine Bedard, MSc, Sara Gonias Murray, MD, and Jennie Ling also participated in this research at Gladstone. Funding came from a variety of sources, including the National Multiple Sclerosis Society, the American Heart Association, the Howard Hughes Medical Institute, the Nancy Davis Foundation for Multiple Sclerosis, the Dana Program in Brain and Immuno-Imaging, H. Lundbeck A/S and the National Institutes of Health.
About the Gladstone Institutes
Gladstone is an independent and nonprofit biomedical-research organization dedicated to accelerating the pace of scientific discovery and innovation to prevent, treat and cure cardiovascular, viral and neurological diseases. Gladstone is affiliated with the University of California, San Francisco.
Gladstone scientists identify key biological mechanism in multiple sclerosis
Cutting-edge imaging study finds potential new target to combat disease
2012-11-30
ELSE PRESS RELEASES FROM THIS DATE:
A multi-wavelength view of radio galaxy Hercules A
2012-11-30
VIDEO:
Spectacular jets powered by the gravitational energy of a supermassive black hole in the core of the elliptical galaxy Hercules A illustrate the combined imaging power of two of astronomy's...
Click here for more information.
Spectacular jets powered by the gravitational energy of a super massive black hole in the core of the elliptical galaxy Hercules A illustrate the combined imaging power of two of astronomy's cutting-edge tools, the Hubble Space Telescope's ...
Mediation with art therapy can change your brain and lower anxiety
2012-11-30
(PHILADELPHIA) – Cancer and stress go hand-in-hand, and high stress levels can lead to poorer health outcomes in cancer patients. The Jefferson-Myrna Brind Center of Integrative Medicine combined creative art therapy with a Mindfulness-based Stress Reduction (MBSR) program for women with breast cancer and showed changes in brain activity associated with lower stress and anxiety after the eight-week program. Their new study appears in the December issue of the journal Stress and Health.
Daniel Monti, MD, director of the Jefferson-Myrna Brind Center of Integrative Medicine ...
Birds may spread, not halt, fever-bearing ticks
2012-11-30
SALT LAKE CITY, Nov. 30, 2012 – Turkey raises and releases thousands of non-native guineafowl to eat ticks that carry the deadly Crimean-Congo hemorrhagic fever virus. Yet research suggests guineafowl eat few ticks, but carry the parasites on their feathers, possibly spreading the disease they were meant to stop, says a Turkish biologist working at the University of Utah.
"They are introducing a species that is not eating many ticks, based on studies of stomach content, and is carrying the ticks, which are the best conduit for spreading Crimean-Congo hemorrhagic fever," ...
Obese children more vulnerable to food advertising
2012-11-30
Cincinnati, OH, November 30, 2012 -- Rates of childhood obesity have tripled in the past 30 years, and food marketing has been implicated as one factor contributing to this trend. Every year, companies spend more than $10 billion in the US marketing their food and beverages to children; 98% of the food products advertised to children on television are high in fat, sugar, or sodium. In a new study scheduled for publication in The Journal of Pediatrics, researchers used neuroimaging to study the effects of food logos on obese and healthy weight children.
Amanda S. Bruce, ...
More neurologists and neurosurgeons are associated with fewer deaths from strokes in the US
2012-11-30
Charlottesville, VA (November 30, 2012). Researchers at Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire, have found an association in the United States between a higher density of neurologists and neurosurgeons and a decreased risk of death from stroke. The findings of their study are described in the article "Association of a higher density of specialist neuroscience providers with fewer deaths from stroke in the United States population. Clinical article," by Atman Desai, M.D., and colleagues, published today online, ahead of print, in the Journal of Neurosurgery. ...
Concussion and its association with contact sports
2012-11-30
Charlottesville, VA (November 30, 2012). The JNS Publishing Group is pleased to announce that the December issue of Neurosurgical Focus is dedicated to Concussion: Pathophysiology & Sequelae. Guest editors Paul S. Echlin (Elliott Sports Medicine Clinic, Burlington, ON, Canada), M. Sean Grady (University of Pennsylvania, Philadelphia, PA), and Shelly D. Timmons (Geisinger Medical Center/Neurosurgery, Danville, PA) selected 11 articles for this issue that focus on methods of diagnosing concussion and evaluating its consequences, structural and functional changes that can ...
Employee Sues Clothing Retailer For Racial Discrimination
2012-11-30
Employee sues clothing retailer for racial discrimination
A former employee of a clothing chain is suing the company for racial discrimination, alleging that she was fired from her job for being African American.
According to the complaint, the employee overheard the executive vice president of the company telling her district manager that the employee "wasn't the right fit for the store" and that it would be preferable to hire someone "with blond hair and blue eyes." The employee says she was fired from her position soon after that conversation.
Allegedly, ...
Facebook Increasingly Tied to Divorce
2012-11-30
Facebook Increasingly Tied to Divorce
Facebook and other social media websites have become integrated into the everyday lives of most Americans. Some keep in touch with loved ones far away, others keep friends and family up to date on their daily lives and some use social media to network with individuals in their field of work. The use of social media does not always have positive results, however. For example, a recent study uncovered that approximately one-third of divorces filed in the United States today mention the word "Facebook."
Social Media Used ...
Safe Driving Tips For Winter Weather In Massachusetts
2012-11-30
Safe driving tips for winter weather in Massachusetts
Cold winter weather can often be accompanied by dangerous driving situations, and it is especially important to keep safety in mind when driving during the winter months. While driving in snow and ice can be nerve wracking, there are many precautions a driver can take to increase safety.
Perhaps the most important thing to remember during the winter months is that a person should only drive when it's absolutely necessary. Avoiding driving when the weather is extreme is the easiest way to stay safe. However, if ...
New York's Domestic Incident Report Repository is Live, Raising Concerns
2012-11-30
New York's Domestic Incident Report Repository is live, raising concerns
Law enforcement officials, legislators, state prosecutors and victims' advocates are hailing New York's new electronic Domestic Incident Report Repository as a win for the state. However, advocates of the DIRR may overlook the negative implications the database may have on those included on domestic reports, including those accused of committing domestic violence and those who are innocent but implicated in a report.
What is the Domestic Incident Report Repository?
The Domestic Incident Report ...
LAST 30 PRESS RELEASES:
Multi-resistance in bacteria predicted by AI model
Tinker Tots: A citizen science project to explore ethical dilemmas in embryo selection
Sensing sickness
Cost to build multifamily housing in California more than twice as high as in Texas
Program takes aim at drinking, unsafe sex, and sexual assault on college campuses
Inability to pay for healthcare reaches record high in U.S.
Science ‘storytelling’ urgently needed amid climate and biodiversity crisis
KAIST Develops Retinal Therapy to Restore Lost Vision
Adipocyte-hepatocyte signaling mechanism uncovered in endoplasmic reticulum stress response
Mammals were adapting from life in the trees to living on the ground before dinosaur-killing asteroid
Low LDL cholesterol levels linked to reduced risk of dementia
Thickening of the eye’s retina associated with greater risk and severity of postoperative delirium in older patients
Almost one in ten people surveyed report having been harmed by the NHS in the last three years
Enhancing light control with complex frequency excitations
New research finds novel drug target for acute myeloid leukemia, bringing hope for cancer patients
New insight into factors associated with a common disease among dogs and humans
Illuminating single atoms for sustainable propylene production
New study finds Rocky Mountain snow contamination
Study examines lactation in critically ill patients
UVA Engineering Dean Jennifer West earns AIMBE’s 2025 Pierre Galletti Award
Doubling down on metasurfaces
New Cedars-Sinai study shows how specialized diet can improve gut disorders
Making moves and hitting the breaks: Owl journeys surprise researchers in western Montana
PKU Scientists simulate the origin and evolution of the North Atlantic Oscillation
ICRAFT breakthrough: Unlocking A20’s dual role in cancer immunotherapy
How VR technology is changing the game for Alzheimer’s disease
A borrowed bacterial gene allowed some marine diatoms to live on a seaweed diet
Balance between two competing nerve proteins deters symptoms of autism in mice
Use of antifungals in agriculture may increase resistance in an infectious yeast
Awareness grows of cancer risk from alcohol consumption, survey finds
[Press-News.org] Gladstone scientists identify key biological mechanism in multiple sclerosisCutting-edge imaging study finds potential new target to combat disease