Knut suffered from a brain inflammation, almost definitely caused by anti-NMDA receptor encephalitis - a disease in which antibodies attack healthy nerve cells in the brain - said wild animal specialist Alex Greenwood and neuroscientist Harald Prüß on Thursday.
This discovery could help scientists treat the autoimmune condition in both animals and humans, reports Tagesspiegel.
Born in captivity in Berlin Zoo, Knut the polar bear was raised by keepers after being rejected by his mother.
The cub quickly became famous, and on March 23rd 2007, over 400 journalists gathered at Berlin Zoo as Knut was presented to the public for the first time.
The day was dubbed "Knut day" – and the cub went on to spawn a mass media phenomenon later called "Knutmania," attracting millions of visitors to Berlin Zoo and bringing in an estimated €5 million in revenue.
But in 2011, Knut collapsed into a water ditch in front of visitors.
The bear had suffered an epileptic fit, and sadly drowned before keepers could come to his aid.
An immediate autopsy showed that Knut's brain was inflamed – a condition known as encephalitis – but vets couldn't determine the cause.
Knut's "foster father" was zookeeper Thomas Dörflein, who passed away in 2008. Photo: DPA
One in 200,000 humans affected
Neuroscientist Prüß first discovered that Knut suffered from anti-NMDA receptor encephalitis.
After years of treating the condition in humans, Prüß noticed some parallels in Knut's symptoms. Further tests confirmed his suspicions.
Anti-NMDA receptor encephalitis affects around one in 200,000 humans every year.
The condition is caused by antibodies produced by the body itself, to fight viruses and infections. But in patients with the condition, the antibodies mistakenly begin to attack nerve cells in the brain.
The antibodies latch onto NMDA receptors in the brain, blocking vital signals and disrupting mental functions.
This particularly disrupts the control centre for memory and learning, said Prüß.
Greenwood, from Berlin's Leibniz Institute for Zoo and Wildlife Research, has been working on establishing Knut's cause of death for four years.
Relieved to discover that, in spite of speculation, it was neither Knut's living conditions nor stress levels that made the bear ill, he stated: "it was all down to nature."
In most human cases, scientists struggle to find a reason for the antibodies being produced, said Prüß.
The condition primarily affects women – and, he explained, is often discovered in women suffering from ovarian cancer or growths.
It's possible that the antibodies are produced to fight these tumours, he said. But as the condition is also found in those who don't have ovarian growths, it's hard to isolate one cause.
Both Prüß and Greenwood hope that the publicity surrounding Knut's life and death could help raise awareness of anti-NMDA receptor encephalitis, leading to faster diagnosis and treatment in both humans and animals.
"The faster immunotherapy can begin, the greater the protection," said Prüß.