Thursday, July 31, 2014

Retraction Of Major Narcolepsy – Autoimmune Link Paper


Photo Credit CDCSleep and Sleep Disorders


# 8897


In August of 2010, roughly 9 months after the first vaccines for the pandemic H1N1 virus became available, we began to see reports of an increase in narcolepsy among children and adolescents in Northern Europe who had received a specific formulation of the vaccine; GSK’s Pandemrix ® (see Finland Suspends Use of Pandemrix Vaccine). 


In February of 2011, the Finnish National Institute for Health and Welfare released an interim report on what they  called  `a probable link’ between GSK’s Pandemrix vaccination, and an increase in narcolepsy in children and adolescents 4-19 years of age.  Two findings of note were:


  • While the Pandemrix vaccine was taken by 31 million people across 47 countries, other than Finland, Sweden and Iceland, no other countries reported an increase in narcolepsy in 2010. 
  • Iceland, unlike Finland, reported an increase in narcolepsy among unvaccinated children during this same time period.


As it turns out, Iceland wasn’t alone in seeing a spike in narcolepsy after the first pandemic wave, as a Stanford study appeared in August of 2011 in the Annals of Neurology called  "Narcolepsy Onset is Seasonal and Increased Following the H1N1 Pandemic in China", among a population who never received the flu vaccine.


While the cause of narcolepsy remains a mystery, it has long been  assumed to be an auto-immune disease, and so seeing spikes following a novel flu pandemic – or even  vaccination – made sense. Narcolepsy is probably more common than most people realize, with its prevalence estimated at being between 25 and 50 per 100,000 people.

The narcolepsy-Pandemrix link story continued with a series of studies and reports that found a link between the two, but not a cause.  While still a mystery, the point became somewhat moot, since Pandemrix was no longer in use.


That is, until December of 2013 when Immunologist Elizabeth Mellins and narcolepsy researcher Emmanuel Mignot at Stanford University School of Medicine published a paper in Science Translational Medicine  (Link) that was hailed as major breakthrough (see Ed Yong’s report in  Nature Narcolepsy confirmed as autoimmune disease) in understanding the disease.

Although I’m badly over-simplifying a complex paper, the authors found that a protein found in the brain – hypocretin – which helps keep us alert and awake, was similar enough to a protein in the H1N1 virus that the body’s immune system could occasionally mistake it for the virus and send T cells to destroy hypocretin-secreting-neurons, thus inducing narcolepsy.


This concept, known as molecular mimicry”, was an elegant explanation, and was widely reported in the academic and mainstream press.  It also suggested that other infections could trigger similar reactions. 

That is, until yesterday when the paper was retracted by the authors.

This from  Stanford Medical News.


Stanford researchers retract study examining link between narcolepsy, H1N1

Stanford researchers have retracted a 2013 study that described a possible immunological connection between narcolepsy and the H1N1 influenza virus.

Jul 30 2014

A paper published Dec. 18, 2013, in Science Translational Medicine that described a possible immunological connection between narcolepsy and the H1N1 influenza virus is being retracted at the request of the authors at the Stanford University School of Medicine.

Sleep researcher Emmanuel Mignot, MD, PhD, a professor of psychiatry and behavioral sciences, and his co-authors requested the retraction because they were unable to replicate some of the results reported in the paper.

The journal published the retraction notice online today.


While this retraction doesn’t invalidate the theory that `molecular mimicry’ plays a role in the development of narcolepsy, it is now far from `confirmed’ as earlier reports indicated.


In a perfect world, the conclusions drawn from scientific research would always be unequivocal and we would be able to automatically accept their results as being the final word on any  subject.  But no research methodology is perfect, all studies are subject to limitations, and it isn’t unusual to end up with conflicting results from different research teams.


Science is often messy and there are few `Eureka!’ moments of sudden clarity. We usually get to the truth by fits and starts – and that can often take years or even decades to sort out.  


For some earlier blogs on the vagaries of research results, you may wish to revisit:


When Studies Collide 

When Studies Collide (Revisited)

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