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Mystery of polar bear Knut's disease finally solved

The animal suffered from an autoimmune disease previously known only in humans

( 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 Charite - Universitaetsmedizin 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.

Cooperation of neuroscientists and wildlife researchers

Dr Harald Pruess, who is a researcher at the Berlin site of the DZNE and a specialist in neurology at the Charite, 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 non-infectious cause of disease, but until the collaboration with Pruess 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 Pruess. 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", Pruess 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 Pruess, 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 anti-NMDA 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."

"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 Pruess.

"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 Charite - 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 Knieriem, Director of the Berlin Zoological Garden.


Original publication Pruess H, Leubner J, Wenke NK, Czirjak GA, Szentiks CA, Greenwood AD (2015): Anti-NMDA Receptor Encephalitis in the Polar Bear (Ursus maritimus) Knut. SCIENTIFIC REPORTS, doi: 10.1038/srep12805.


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