Thursday, November 19, 2009

Advances in Spongiform Encephalopathy

Well into the 1970s, members of the Fore tribe of Papua New Guinea were afflicted by a devastating neuro-degenerative epidemic known as kuru. The disease shares considerable similarity with spongiform encephalopathy first described by the German physician/scientists Hans Gerhard Creutzfeldt and Alfons Maria Jakob in the 1920s, CJD for short. Often more than a decade after infection, the afflicted develop conspicuous trembling and severe motor dysfunction as a consequence of progressive nerve cell death in the central nervous system. The video below portrays the symptoms of this horrible disease graphically. Some readers may find the footage disconcerting.

As a consequence of nerve cell degeneration, the brain tissue shrinks in places. Microscopic holes pockmark the tissue like a sponge in histological preparations.

Kuru may have been acquired through the inheritance of defective genes. Isolated tight-knit island communities like the tribes of Papua New Guinea are known to be particularly vulnerable to inheritable genetic defects because of their limited gene pools. Indeed, genetic mutations seem to cause spongiform encephalopathy. Recently, Wang and others (2008) provided evidence for the underlying molecular mechanisms.

Peculiarly, among the Fore of Papua New Guinea particularly women and children developed kuru. The Fore were known to ingest the bodies of deceased loved ones during funeral rites in order to capture their life forces. Women and children ate mainly brain parts. Perhaps the origin of the disease was passed along with the brain tissue. In support of this idea, the late American Nobel Prize-laureate Daniel Carleton Gajdusek proved that kuru was indeed an infectious disease that could be transmitted even to other primates. Curtailing cannibalism on the islands would drastically reduce the occurrence of the disease.

Years later, Stanley Prusiner would win the Nobel Prize for ultimately identifying the molecular basis of the transmitted variant of spongiform encephalopathy. The infectious agent was not an organism. Nerve cells incorporated misfolded proteins known as prions that attached to native forms of functional cellular proteins, forcing them to undergo a similar conformational change. Like a snowball, the dysfunctional protein grows forming amyloid plaques that eventually destroy the cells.

Misfolded prions are fairly stable, temperature resistant molecules, remaining active even in soil outdoors for decades. Scrapies, which causes spongiform encephalopathy among sheep and goats, is believed to be contracted through fodder contaminated with urine and feces from infected animals.  Bovine spongiform encephalopathy (BSE), popularly known as Mad Cow Disease, has been shown to be transmitted by protein-enriched power feed contaminated with prions. Beef from infected cattle may cause CJD in people.

Remarkably, however, some highly-exposed Fore remained unaffected by kuru. In this week's issue of the New England Journal of Medicine, researchers at University College of London report that they found a new variant of the gene PRNP encoding prion protein that is unique to the resilient tribal members and may improve resistance to the disease (Mead and others, 2009). The newly discovered genetic variant, called G127V, appears to render the native prion protein less pliable to conformational change induced by misfolded protein. It was detected in half of the women who were homozygotes for an already known resilience factor. That is, they possessed identical variants of PRNP on both chromosomes carrying the gene. By contrast, tribespeople who succombed to kuru did not possess this variant, and it is absent from the global human population unexposed to the disease.

This discovery does not only open new avenues for the treatment of spongiform encephalopathy, but moreover further affirms genotypal variation and phenotypal selection as fundamental evolutionary forces that affect all living things as Charles Darwin proposed in his theory published in "On the Origin of Species" almost to the day 150 years ago. Darwin would have been delighted to learn about this finding, particularly in the year of his 200th birthday.

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1 comment:







    =Y of or X=

    The Sublet of the Genetic Substance,
    Is the Rise of the Hypothesis, of and for the sublet of your rising design of your design of your Immune system.
    This being said we are the process of information around the Galaxy, to and from the Heaven to your Hell, in the process of the Genetic code is the eyes and ears of your immune system, this being said when we understand and formulate the system of R(sq)(I(sq))(N(sq))(T(sq))(V(sq))= the immunionic code system of the desire of the demunning the system of the immunning Hypothisis.
    This being said we are immuning the Genetic code instead of immunning the Imuninal code of the sublet versus the design of the original design system.

    R=resistance of the germs or virus
    I=the immune system of the red/the ionic reaction of the white blood cell counts
    N=nerve endings of the triggering the immune system to react to the barometric pressure of the DNA
    T=Serum the blood excursions to secrete the miracle of life upon the viral attack system
    V=the Anti/bodies the membrane secretes, through the tough shell of the capillaries to the, Blood vessels.
    Is not defined of security, to fine the memory genetic secretions, past the immoral, genetic programming, and focus, in the bio-logical secretions, of the binary incisions’, beneath the crusted layers of the genetic substance by performing a microscopic, telephonic technological picture of the mannerism of the biological functions, of the mirror cascading the cellular dysfunction, in a new instrumentation, to the very essence of the immune bio-plexities, past the dysfunctional chemical imbalances, of the cerebral cortex, to see past the dysfunction and see the functional subjective means of the placebo, past the hypocrisy of stem cell research facilities, who desperately finding means to formulate tradition microscopic discoveries.