TORONTO - Infection with some kinds of influenza viruses may set up people to be at higher risk of developing Parkinson's disease later in life, a new American study suggests.
The work, inspired by the story behind the 1990 movie "Awakenings," suggests some aggressive strains of flu that can pass into the brain may deplete dopamine-creating neurons, leaving a person more vulnerable to developing the neurodegenerative disease at a later date.
"I am very confident (that) ... viruses will be considered a player in the etiology of PD (Parkinson's disease)," said senior author Dr. Richard Smeyne, a neurologist and neuroscientist at St. Jude Children's Research Hospital in Memphis, Tenn.
"Not a direct cause, but maybe the initiating cause... It sets you up."
"Awakenings" was the story of how American neurologist Oliver Sacks figured out he could revive people suffering from a strange sleeping sickness called encephalitis letharagica or von Economo's encephalopathy using the newly discovered Parkinson's drug L-dopa.
An epidemic of von Economo's encephalopathy in parts of Europe and in North America was recorded from about 1915 to 1926. A couple of decades later some of the survivors of the event descended into a catatonic state which Sacks correctly identified as Parkinsonian.
The overlap of the initial outbreak with the 1918 Spanish flu led some people to conclude infection with that virulent virus was the trigger for the illness.
Smeyne has been studying whether there is a viral component to the development of Parkinson's disease. Unusual clusters of cases have led researchers to believe exposures to environmental agents like pesticides or bacterial or viral infections may contribute to the development of Parkinson's in some people.
The most famous of the clusters involved a Vancouver TV show in the late 1970s on which a young Michael J. Fox worked. Fox and several other members of the production developed Parkinson's at an early age.
In discussions with colleagues in St. Jude's renown influenza research team, Smeyne and his team decided to look at whether influenza viruses might be one such trigger using another highly virulent flu virus -- the H5N1 avian flu variety. A co-author of the paper is Dr. Robert Webster, a leading figure in the world of influenza.
The article, published in the Proceedings of the National Academy of Sciences, traced the entry and progression of the H5N1 avian flu virus in the brains of infected mice. The scientists found the aggressive H5N1 virus killed about 17 per cent of dopamine-creating neurons.
Smeyne said a corresponding loss in humans -- if it occurs -- wouldn't be enough to trigger Parkinson's on its own. But it could predispose a person to be more vulnerable to developing it, or speed up the point in life at which someone might develop the neurodegenerative disease, he said.
An expert on the virus that caused the Spanish flu, Dr. Jeffery Taubenberger, said the study raises an interesting hypothesis, but does not answer the question of whether flu viruses play a role in the development of Parkinson's.
"I think that it's certainly interesting to think about ... certain viruses that might be able to replicate in neuronal cells as an example of something that could lead to an insult, a physical insult, that could lead to some kind of neurodegeneration," said Taubenberger, an influenza researcher at the U.S. National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health.
"But I think that it is a bit extreme to take a mouse study and then say that there might be a link in humans to Alzheimer's or Parkinson's disease."
Taubenberger, who led a team that excavated viral remnants of the virus that caused the Spanish flu and then sequenced the virus, said a sort of mythology has encompassed the 1918 virus, ascribing to it powers it probably did not have.
Work he has done looking at whether the virus was responsible for the epidemic of von Economo's encephalopathy does not support a link, he said. He and his team have studied preserved brain tissues of people who suffered from the condition, looking for traces of viral RNA. They found nothing.
They also looked at whether the 1918 virus travels into the brain when mice are experimentally infected with it. It does not. The combined work, Taubenberger said, led his team to conclude the data don't support a strong link between the 1918 flu and the outbreak of von Economo's encephalopathy.
He suggested a study of survivors of H5N1 infection could shed light on whether they suffer any neurological or neurodegenerative conditions that might be linked to that virus.
Smeyne said the neurodegenerative aspect his team sees with H5N1 probably does not exist for all flu viruses and may not be true for the milder swine flu or H1N1 virus causing the current flu pandemic.
"It's a fairly mild form of influenza. There doesn't seem to be encephalitis associated with it," he said.
"That would suggest we would not see it (crossing into the brain). But I think without the direct experimental evidence which we need to look at, I think that we can't say one way or the other at this point."
