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German Center for Neurodegenerative Diseases (DZNE) Holbeinstraße 13-15 53175 Bonn Germany Press Embargo: 27.08.2015, 3 PM CEST Dr Marcus Neitzert Science Editor Phone:+49 228/43302 271 [email protected] www.dzne.de Press Release Mystery of polar bear Knut’s disease finally solved The animal suffered from an autoimmune disease previously known only in humans. Leibniz Institute for Zoo and Wildlife Research (IZW) Alfred-Kowalke-Str. 17 10315 Berlin Germany Steven Seet Head of Unit Press & Communications Phone: +49 30/5168 125 Mobile:+49 177 857 26 73 [email protected] www.leibniz-izw.de Berlin, 27th August 2015 Knut, the famous polar bear of the Berlin Zoological Garden (Germany) died of encephalitis, as diagnosed soon after his death. However, the cause of his disease has remained elusive until now. A team of scientists from the German Center for Neurodegenerative Diseases (DZNE), the Leibniz Institute for Zoo and Wildlife Research (IZW) and the Charité Universitätsmedizin Berlin has now solved the case: The polar bear suffered from an autoimmune disease of the brain. This non-infectious illness is called “anti-NMDA receptor encephalitis”, with symptoms in human patients similar to those displayed by Knut. Knut is the first wild or domestic animal in which this form of encephalitis has been demonstrated. The results were reported in the scientific journal “Scientific Reports”. The authors propose that errant immune responses may be associated with brain diseases more commonly than previously assumed. Knut was a favourite with the public across the world and became well known far beyond the borders of Berlin. The polar bear drowned on 19th March 2011 after suffering epileptic seizures and falling into the enclosure pool. Scientists under the leadership of the IZW intensively investigated the potential causes of Knut’s death and revealed that the seizures were caused by encephalitis, suspecting an infection by an unknown pathogen. The exact cause of the disease remained a mystery. 1 Charité – Universitätsmedizin Berlin Charitéplatz 1 10117 Berlin Germany Manuela Zingl Deputy Press Spokesperson Phone: +49 30/450 570 400 [email protected] www.charite.de Zoologischer Garten Berlin AG Hardenbergplatz 8 10787 Berlin Germany Christiane Reiss Phone:+49 30/25401 221 [email protected] www.zoo-berlin.de Cooperation of neuroscientists and wildlife researchers Dr Harald Prüß, who is a researcher at the Berlin site of the DZNE and a specialist in neurology at the Charité, read the autopsy report and discovered parallels to his own studies on human brain diseases. The neuroscientist contacted Prof Alex Greenwood, leader of the Department of Wildlife Diseases at the IZW. Could it be possible that Knut might have suffered from an autoimmune disease of the brain? The two scientists quickly agreed to follow up this line of research together. Greenwood, head of the primary study on Knut, had considered that there might be noninfectious cause of disease, but until the collaboration with Prüß there was no real possibility to test for this class of diseases in wild animals. The IZW had stored samples of the polar bear’s brain which were now used for analysis. "This study provided us with the possibility to extend and refine our test methods", says Prüß. The analysis revealed that the polar bear had developed "anti-NMDA receptor encephalitis". In the tissue samples of the animal, the scientists demonstrated the presence of NMDA-receptor antibodies, the characteristic proteins for this encephalitis. "Until now, this autoimmune disease has only been known in humans. In this illness, the body’s immune system overreacts and produces antibodies which damage nerve cells instead of fighting against pathogens", Prüß explains. "Epileptic seizures, hallucinations and dementia are among the possible symptoms." Until recently unknown These diseases were discovered only a few years ago. According to Prüß, until recently, patients with encephalitis for which viruses or bacteria were not identified as causative agent remained undiagnosed, and their origin a mystery. “In the past few years, the number of unsolved cases has decreased considerably. Since 2010, we have known that the majority of patients with encephalitis of unknown etiology are suffering from antiNMDA receptor encephalitis, once infectious causes were ruled out. There are now standard tests to diagnose the disease”, says the neuroscientist. “In humans this disease is relatively responsive to medical treatment.” 2 “We were quite intrigued by this result”, comments IZW scientist Greenwood on this discovery. “The anti-NMDA receptor encephalitis has been described only very recently in humans. Clearly it is also of importance for other mammals. We are relieved to have finally solved the mystery of Knut’s disease, especially as these insights could have practical applications. If the current therapy for human patients is also suitable for wild animals, many cases of fatal encephalitis in zoos may be prevented in future.” Antibody tests in dementia patients “Knut’s disease has further implications. It is possible that autoimmune diseases of the nervous system might be far more common in humans and other mammals than previously assumed”, says Greenwood. “We might underdiagnose autoimmune inflammations in human patients suffering psychoses or memory disturbances, because these patients are not routinely screened for associated antibodies. As a result they may not receive the optimal treatment. Therefore, I believe it is reasonable to examine patients for associated antibodies, especially if the cause of a dementia is unknown. These antibodies can be held in check by pharmaceutical means. There are also other forms of encephalitis, where errant antibodies against other receptor molecules are important in disease development”, comments DZNE researcher Prüß. „The research results are an important contribution to understanding autoimmune diseases of the nervous systems in animals. One can only congratulate the scientists of the German Center for Neurodegenerative Diseases, the German Leibniz Institute for Zoo and Wildlife Research and the Charité - Universitätsmedizin Berlin. They have made it possible that in the future, diseases in animals similar to Knut’s could be diagnosed earlier and treated”, says Dr Andreas Knierim, Director of the Berlin Zoological Garden. Original publication Prüss H, Leubner J, Wenke NK, Czirják GÁ, Szentiks CA, Greenwood AD (2015): Anti-NMDA Receptor Encephalitis in the Polar Bear (Ursus maritimus) Knut. SCIENTIFIC REPORTS, doi: 10.1038/srep12805. 3 Photos (caption) 01-03: Knut 2007, author: Zoo Berlin/04: Knut 2008, author: Zoo Berlin/05: Knut with encephalitis, authors: DZNE, IZW & Zoo Berlin. Download link (20 MB): http://www.zoovet-conference.org/knut/knut.zip Press Conference Meet the experts on 27th of August 2015, 11.00 am – 13.00 pm CEST at Schloss Friedrichsfeld in the “Tierpark Berlin”, Am Tierpark 125, 10319 Berlin, Germany. All information at the press conference will be under embargo till 3.00 pm CEST. Contact: Steven Seet; +49 177 857 26 73; [email protected]. The German Center for Neurodegenerative Diseases (DZNE) investigates the causes of diseases of the nervous system and develops strategies for prevention, treatment and care. It is a cross-institutional network under the leadership of the Helmholtz Association of German Research Centres with sites in Berlin, Bonn, Dresden, Göttingen, Magdeburg, Munich, Rostock/Greifswald, Tübingen and Witten. The DZNE cooperates closely with universities, their clinics and other research facilities. www.dzne.de www.twitter.com/dzne_en www.dzne.de/facebook The Leibniz Institute for Zoo and Wildlife Research (IZW) investigates the vitality and adaptability of wildlife populations in mammalian and avian species of outstanding ecological interest that face anthropogenic challenges. It studies the adaptive value of traits in the life cycle of wildlife, wildlife diseases and clarifies the biological basis and development of methods for the protection of threatened species. Such knowledge is a precondition for a scientifically based approach to conservation and for the development of concepts for the ecologically sustainable use of natural resources. The IZW belongs to the Forschungsverbund Berlin e.V. (www.fv-berlin.de) and the Leibniz Association (www.leibniz-gemeinschaft.de). www.izw-berlin.de The Charité is one of the largest university hospitals in Europe. Here, 3700 doctors and scientists heal, do research and teach at the top international level. More than half of the German Nobel Prize winners in medicine and physiology come from the Charité, among them Emil von Behring, Robert Koch and Paul Ehrlich. The Charité also has an international reputation for excellence in training. It extends over four campuses with almost 100 clinics and institutes bundled under 17 CharitéCenters. With 13,100 employees, the Charité generates about 1.5 billion euros in sales per year and is one of the largest employers in Berlin. In 2010, the Charité could look back and joyously celebrated its 300-year anniversary. Encephalitis and Paraneoplasia Consultation Hours at the Department of Neurology with Experimental Neurology of the Charité: http://neurologie.charite.de/patienten/hochschulambulanzen/enzephalitis_und_paraneopla sien/ www.charite.de 4 Since it opened in 1844, the Zoo Berlin is considered to be Germany’s number one zoological garden and currently represents more species than any other zoo in the world. Over 17,000 animals from close to 1,500 species live right in the heart of Berlin, in its zoo and aquarium. Besides unusual and exotic animals, such as kiwis and axolotl, the Zoo Berlin is home to many endangered species as well as rare domestic breeds. The Tierpark Berlin, in the eastern part of the city, also belongs to the Zoologischer Garten Berlin AG. Over 7,000 exotic animals from 815 species are at home here in Europe’s largest wildlife park, where they live in spacious and diversified parkland. The number of visitors is also unique in Europe: more than 4.4 million guests visit the Zoo Berlin AG every year. www.zoo-berlin.de, www.tierpark-berlin.de 5