For the first time, Researchers at the Cells-in-Motion Cluster of Excellence (CiM) at Münster University have been able to image ongoing inflammation in the brain of patients suffering from multiple sclerosis.
The ultimate aim in biomedical research is the transfer of results from experiments carried out in animals to patients. Researchers at the Cells-in-Motion Cluster of Excellence (CiM) at the University of Münster have succeeded in doing so.
For the first time, they have been able to image ongoing inflammation in the brain of patients suffering from multiple sclerosis (MS). This involved specialists from different disciplines working together in a unique way over several years, combining immunology, neurology and imaging technologies ranging from microscopy to whole-body imaging.
The consequences of an inflammation in the brain can already be shown using a clinically established process: magnetic resonance imaging (MRI). Making the inflammation itself visible too could, in future, help not only to more accurately diagnose multiple sclerosis patients but also to monitor therapies and apply them in a more specific way. The study has been published in the prestigious journal "Science Translational Medicine".
Occurring mostly in sporadic attacks, the flares associated with multiple sclerosis cause patients considerable discomfort. In this autoimmune disease, immune cells – in other words, cells from the body's own defence system – target the very organism they are supposed to protect. To do so, they must first penetrate the so-called blood-brain barrier to then be able to attack the central nervous system.
For the first time, CiM researchers have used certain enzymes – matrix metalloproteinases (MMPs) – to image inflammation in the brain that typically occurs during flares in MS patients. In a preliminary study, biologists and biochemists in a team headed by CiM Spokesperson Prof. Lydia Sorokin discovered that these enzymes play a pivotal role. They had investigated mice with a similar disease to MS and found that MMPs are essential for immune cell penetration of the blood-brain barrier and their migration into the brain, where they cause inflammation.
In order to label these enzymes in the brain and visualize them through specialized imaging techniques, a team of chemists and nuclear medicine specialists headed by one of CiM Coordinators, Prof. Michael Schäfers, developed a tracer – a chemical substance that tracks down the active enzymes in the body and binds to them. The chemists linked the MMP tracer with a fluorescent dye. The fluorescence light signals from such a tracer can be measured using optical imaging techniques. Via the tracer signal the researchers were able to localize and measure the activity of the enzymes, initially in mice. "We found that our observations of MMP activity provided precise information on where immune cells penetrate the blood-brain barrier and where inflammation occurs in the brain," says Dr. Hanna Gerwien, a molecular biologist.
First case studies with patients
The researchers have now succeeded in transferring the method to humans. However, it was not possible to use the fluorescent tracer because its light signal would not penetrate the skull of a patient. The researchers therefore modified the tracer, adding a radioactive signal transmitter instead of a fluorescent dye. The radiation it emits can be measured and made visible using a special method, positron emission tomography (PET). Nuclear medicine specialists and neurologists at the Cluster of Excellence in Münster (who also work at Münster University Hospital) have now carried out the first case studies on MS patients. The result was that in patients with acute attacks of MS the tracer accumulated clearly in defined areas, even before any damage to the blood-brain barrier could be measured using the traditional method, magnetic resonance imaging.
"It really was something special to be able to corroborate something in a patient that had already discovered in basic research in experiments on animals," says Dr. Sven Hermann, an expert in nuclear medicine and small animal imaging, "it's what every scientist dreams of". The scientists also observed, as they predicted, that little or no tracer accumulated after the patients had undergone anti-inflammatory therapy.
The investigation described here is a pilot study. This process has not been used in clinical practice. The work was supported by the Cells-in-Motion Cluster of Excellence, the Collaborative Research Centre 656 "Molecular Cardiovascular Imaging" and the Collaborative Research Centre TR-128 "Multiple Sclerosis" at the University of Münster.
Gerwien H*, Hermann S*, Zhang X, Korpos E, Song J, Kopka K, Faust A, Wenning C, Gross CC, Honold L, Melzer N, Opdenakker G, Wiendl H, Schäfers M*, Sorokin L*. Imaging Matrix Metalloproteinase Activity in Multiple Sclerosis as a Specific Marker of Leukocyte Penetration of the Blood-Brain Barrier. Science Translational Medicine, DOI: 10.1126/scitranslmed.aaf8020 (*equal contribution)
Cells-in-Motion Cluster of Excellence/Media contact:
Media Relations Manager
Tel.: +49 251 83-49310
http://www.uni-muenster.de/Cells-in-Motion/newsviews/2016/11-10.html Further information and detailed picture description (CiM webpage)
http://stm.sciencemag.org/content/8/364/364ra152 Original publication
https://www.uni-muenster.de/Cells-in-Motion/de/ "Cells in Motion" Cluster of Excellence
http://www.sciencemag.org/ "Science" Homepage
Dr. Christina Heimken | idw - Informationsdienst Wissenschaft
Microscope measures muscle weakness
16.11.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg
Good preparation is half the digestion
16.11.2018 | Max-Planck-Institut für Stoffwechselforschung
Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.
Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...
Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.
Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...
Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.
In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...
On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.
When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure
Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...
09.11.2018 | Event News
06.11.2018 | Event News
23.10.2018 | Event News
16.11.2018 | Life Sciences
16.11.2018 | Life Sciences
16.11.2018 | Physics and Astronomy