Bovine spongiform encephalopathy also known as “mad cow disease”, is another prion disease that affects cattle, and was responsible for bringing more attention to all of these disorders in the 1990s.
Kuru is confined the Fore tribes of Papua, New Guinea.
In the 1950s there were 2100 cases of Kuru in these tribes leading to about 1000 deaths per year.
As per the culture of the Fore tribe, if a person in a family dies his meat is eaten by his family members, especially the wife and children, as a mark of respect to him. 90% of people affected by the disease were women and children.
Between 1996 to 2004 only 11 new cases of Kuru were identified in the region. Currently with the ban of cannibalism in the Farah tribes the disease had become virtually non existent.
Kuru first presents with tremors, then unsteady gait and progresses to leg weakness, ataxia, incoherent speech, sporadic laughter finally. In later stages, affected patients become demented, bed bound and unable to swallow.
Death occurs most commonly from respiratory distress and pneumonia or infection of pressure sores. The disease is fatal within 1-2 years of the onset of symptoms and had no known cure.
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The causative organism is a prion, a mutated protein which replicates itself like a virus, and is spread by eating the neuronal tissue of infected people.
The precise incubation period of the disease is unknown, but can be up to fifty years.
The pathological hallmark is the presence spongioform encephalopathy with of Prion reactive plaques mostly in the cerebellum:
The detailed studies of theses cases of Kuru has helped us understand other prion diseases such as variant CJD, sporadic CJD whose clinical features and course is similar to this condition.
As far as infectious diseases go, prions are a relatively new discovery. While humanity has known about parasites since ancient times, bacteria since the 1660s, and viruses since 1898, the first prion protein was only isolated in 1984. Since then, we’ve gotten to know a little more about these proteins, and we’ve found that its novelty is by no means the most interesting thing about it. hh hh hh hh
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So what are prions?
Prions are basically the misfolded version of a normal protein, PRP or Protease resistant protein. In the vast majority of instances, the body has mechanisms that adequately deal with misshapen proteins. These get tagged for destruction by antibodies or intracellularly by specific molecular signals and lysosomes. However, prions are not your run of the mill abnormal protein. They are resistant to degradation and exhibit the unique characteristic of causing other normal PRP proteins to misfold, which in turn causes even more misfolding. In this sense, prions behave like protein zombies.
And like zombies, they don’t begin their existence as malevolent molecules either. Indeed this is one of the characteristics which differentiate prions from most other infectious agents such as bacteria or viruses, majority of which are inherently disease causing. Studies have shown that normal PRP has functions in sleep, memory, neural development, and possibly the maintenance of the myelin sheath that surrounds neurons. Indeed, a mutation of PRP causes a very rare disease (only 8 cases have been diagnosed as of 2005) called Familial Fatal Insomnia which leads to progressively worse insomnia leading to dementia, hallucinations, and eventually death.
Yes, complete inability to sleep kills.
hh The connection to Alzheimer’s
Until recently, the most notable examples of prion diseases in humans are Creutzfeldt-Jakob disease and Kuru. Although spontaneous CJD does rarely occur, both these diseases are usually caused by ingestion of infected material, ie, eating infected meat (beef) for CJD and cannibalism for Kuru. Both exhibit progressive dementia, memory problems, gait and movement disturbances, and other unusual symptoms like uncontrolled laughter, hallucinations, and personality changes. Pathologically, the disease causes patients’ brains to develop tiny holes, much like a sponge. Thus the name for the disease in cows, Bovine Spongiform Encephalopathy, literally translates “cow spongy brain disease”.
Brain of a CJD patient with multiple “holes”
However, over the past 5 years, research has shown that at least one major protein known to accumulate in Alzheimers disease, amyloid beta, behaves much like prions. Research conducted at UCSF showed that when mice brains are seeded with amyloid beta, after 300 days, the amyloid plaque is found all over the brain, not just the area seeded. A Yale university study in 2009 also showed that prion proteins of CJD interact with amyloid beta in some way to cause the dysfunction in neurons which lead to Alzheimer’s. Although there is no evidence that AD is contagious, it may open up new therapeutic avenues to think of its pathology as like that of prion diseases.
Amyloid plaques and Neurofibrillary tangles in Alzheimer’s disease
How Alzheimer’s spreads in the brain.
Indeed, last year, a British team accidentally stumbled on a discovery that antibodies designed to treat CJD were found to block Alzheimer’s disease. These antibodies, ICSM-35 and ICSM-18, blocked the interaction between the PRP prion and amyloid beta in mice brains, resulting in decreased hippocampal nerve cell disruption. ICSM-18 and ICSM-35 are presently undergoing human trials for the treatment of CJD. With this finding, it’s likely they will be tested for Alzheimer’s as well, and we, for the first time, might have an effective and specific treatment for this disease which affects roughly 20 million people worldwide.
To see just how significant any form of treatment might be, check out the facts and figures provided by http://www.alz.org below:
References:
Jucker M, Walker LC. Pathogenic protein seeding in Alzheimer disease and other neurodegenerative disorders. 2011:70, 532–540.
Prusiner SB: A unifying role for prions in neurodegenerative diseases. 2012:336, 1511–1513.
Neurology Update 