During his lifetime, it was discovered that Knut, Zoo Berlin's most famous polar bear, had contracted a brain illness of unknown origins. 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 clarified the diagnosis: The polar bear was suffering from an autoimmune disease of the brain. This noncontagious condition called "Anti-NMDA receptor encephalitis" is experienced by humans in a similar form and has been detected in the animal kingdom now for the very first time. The researchers report about the subject in the "Scientific Reports" journal. According to their assessment, misdirected immune responses might be possibly more involved in brain illnesses than previously thought.
Knut was a crowd-pleaser and famous far beyond the boundaries of Berlin. The animal died on 19 March 2011 when he collapsed and drowned in a water ditch within his enclosure as a result of an epileptic seizure. The circumstances of his death were intensively studied by the IZW at the time and it was determined that the trigger of the epileptic seizure was a brain inflammation. An infection was suspected as the trigger, the exact cause of the disease, however, had remained a mystery.
Cooperation of brain and wildlife researchers
When qualified professor Dr. Harald Prüß, scientist at the Berlin office of the DZNE and specialist at the Charité Clinic of Neurology, learned about these findings, he studied the autopsy report and discovered parallels to his own studies of human brain disorders. The neuroscientist consequently got in touch with Prof. Alex Greenwood, Head of the Department of Wildlife Diseases at the IZW. Should Knut have suffered from an autoimmune disease of the brain? Both researchers quickly agreed to look into this presumption more closely. Greenwood, who led the original investigation into Knut, had long considered a non-infection-related encephalitis as the cause. He hadn't, however, had the chance to demonstrate this illness in wild animals before he started collaboration with Prüß. The IZW had kept samples from the polar bear's brain. The researchers could now refer to these.
"These studies gave us the chance to expand and refine our test methods", says Prüß. The analysis showed that the polar bear had fallen ill with "Anti-NMDA receptor encephalitis". The scientists were able to demonstrate typical proteins, so-called antibodies" for this in the tissue samples of the animal.
"This autoimmune disease has only so-far affected humans. The body's immune system "overshoots" the target to a certain extent. Antibodies are released that damage the body's own nerve cells instead of fighting the pathogens," explains Prüß. The possible symptoms include epileptic seizures, hallucinations and dementia."
Unknown until recently
These mechanisms were discovered only a few years ago. Beforehand, we struggled to break down the causes for this brain inflammation in humans, which was not triggered by pathogens such as viruses, bacteria or parasites, according to Prüß. "In the meantime, the number of unsolved cases has dropped significantly. We have known since 2010 that most patients with a brain inflammation are diagnosed with Anti-NMDA receptor encephalitis without detection of pathogens. There are now test methods to detect characteristic antibodies in such a case," comments the neuroscientist. "This illness can be treated relatively well with medicine in humans."
"Ultimately, we were really quite impressed with this result", noted IZW researcher Greenwood on the new findings about Knut's illness. "The anti-NMDA receptor encephalitis was only recently described in humans. But it is clearly also of significance for other animals. We are relieved to have finally solved the mystery of Knut's illness. All the more so that these findings could have practical significance. This illness is treatable in humans. If we succeed in transferring these treatments, then we could possibly treat animals at the zoo with such brain inflammation with a certain degree of success and avoid any deaths."
Antibody tests in dementia patients
"Knut's illness is a further clue in yet another respect: It may be possible that autoimmune diseases of the nervous system in humans and other mammals are more common than previously thought", believes Greenwood.
"It could be that we have overlooked autoimmune-mediated inflammation in humans with psychosis or memory disorders. This is because these patients are not routinely tested for the corresponding antibodies. Consequently, we cannot optimally treat them. I therefore think it is meaningful to test patients for the relevant antibodies, especially when the cause of dementia is unclear. Antibodies are potential targets for drugs. Especially since there are other brain illnesses in addition to Anti-NMDA receptor encephalitis, for which misguided antibodies are also significant", commented DZNE researcher Prüß.
"The present study results are an important contribution to research in terms of issues related to autoimmune diseases of the nervous system in animals. The scientists from the German Center for Neurodegenerative Diseases, the Leibniz Institute for Zoo and Wildlife Research and the Charité - Universitätsmedizin Berlin should be duly congratulated. They have formed the future basis for identifying illnesses like the one found in Knut much more quickly and initiating treatment earlier on", says Dr. Andreas Knieriem, Director of the Zoologischer Garten Berlin.