New Prion Disease?
Fatal Insomnia Linked
To Abnormal Brain Proteins
NEW YORK - A non-inherited form of a rare, fatal insomnia syndrome has joined the list of illnesses thought to be caused by prions (abnormal brain proteins), according to researchers.
"These findings emphasize the need to monitor prion diseases and to assess their potential risks to public health," write Drs. Pierluigi Gambetti and Piero Parchi of Case Western Reserve University, Cleveland, Ohio. Their comments come in response to a study published in the May 27th issue of The New England Journal of Medicine.
Prions are abnormal proteins that appear to trigger a gradual degeneration of brain tissue. Scientists have designated prion activity as a possible cause of at least four rare degenerative brain illnesses " Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker disease, kuru (found in New Guinea tribes that practiced cannibalism), and a genetically-inherited form of fatal chronic insomnia.
Prions are also thought to be responsible for a variant of Creuztfeldt-Jakob disease, the fatal degenerative brain disorder that is similar in progression to the 'mad cow disease' found in cattle.
In this issue of the Journal, researchers led by Dr. James Mastrianni of the University of California, San Francisco, report the first confirmed case of 'sporadic' (non-inherited) fatal insomnia linked to prions.
They describe the case of a 44-year-old man who died after 16 months of severe insomnia, gradually culminating in a loss of motor control, hallucinations, delusions, and respiratory failure.
Post-mortem tests on the patient's brain tissue and DNA testing revealed the presence of prions, but not the genetic abnormalities that are the hallmark of the familial form of fatal insomnia.
In their commentary, Gambetti and Parchi acknowledge that "one might question the establishment of a novel disease on the basis of a single case, but... we have also recently described five patients with similar (disease) features." They believe that this mounting body of evidence "establish(es) the existence of the sporadic form of fatal insomnia," potentially linked to prion activity.
Both the sporadic and familial forms of fatal insomnia appear to be extremely rare disorders. For example, experts have so far only isolated 24 families around the world who seem predisposed to the inherited form of the disease.
Prions - New Brain Disorder Linked To Mad Cow Disease
CHICAGO (AFP) - A new neurological disorder is shedding light on prions, the mysterious, deformed proteins that also cause bovine spongiform encephalopathy (BSE) or "mad cow disease" as well as a variety of related human brain disorders.
The first identified case of sporadic fatal insomnia (SFI), a disease linked to a genetic disorder called fatal familial insomnia (FFI), is spotlighted in the latest issue of the New England Journal of Medicine.
"We found a disease that is indistinguishable from the genetic disorder but lacks the disease gene," said James Mastrianni, a University of Chicago neurologist and lead author of the study.
He said the genetic form was found in only 24 extended families worldwide, while the sporadic form, although still rare, may turn out to be more common.
Symptoms occurred when deformed prions -- caused by irregularities in the folding of a particular protein -- stop functioning, cannot be chewed up by enzymes or eliminated from the brain and gradually accumulate, causing untreatable sleeplessness, loss of coordination, loss of mental function and ultimately death usually within less than two years.
The documented SFI case involves a previously healthy 44-year-old California man whom Mastrianni had treated in San Francisco two years ago for sleep loss.
After four months of sleeping an average of one hour per night, the patient began having trouble walking, lost weight, produced tears excessively, could not swallow properly and gradually lost coordination and short-term memory. Afflicted with severe delusions, he eventually died.
An autopsy of the patient showed brain damage consistent with FFI but no evidence of the abnormal gene in any tissue. There was no prior history of a similar disease in his family.
Mastrianni and colleagues at the University of California then used extracts from the patient's brain and from the brain of an FFI-stricken patient to transmit the disease to transgenic mice that carried a mouse/human prion protein gene.
The symptoms in the affected mice were indistinguishable and the scientists concluded that the strains were identical.
"Even in the familial form, it's the prion strain, and not the variation in the gene that ultimately determines the consequences of the disease," Mastrianni surmised.
SFI is thus part of a wide range of prion diseases that include BSE, its human offshoot known as new variant Creutzfeld-Jakob disease and perhaps more common human brain disorders such as Alzheimer's disease or Parkinson's disease.
Pierluigi Gambetti, a neurologist at Case Western Reserve University in Cleveland, said the findings by Mastrianni's team underscored the need to monitor prion diseases and assess their potential risks to public health.
"Surveillance is required not only to detect novel variants of prion diseases but also to monitor their prevalence and determine whether they are sporadic, inherited or acquired by infection from animals or humans," he said.
In a related development, a Food and Drug Administration (FDA) panel was to meet in Washington next Wednesday to review possible additional steps to protect the US blood supply from exposure to food-borne BSE that could spread new-variant CJD.
The controversial steps under consideration include barring people who lived in Britain or other BSE-affected country during the high-risk period (1980 to 1996) from donating blood or blood products in this country.