NEUROLOGISTS WONDER ABOUT CREUTZFELDT-JAKOBOUTBREAK
By David N. LeffScience Editor
As British beef and dairy farmers bitterly go about destroying fourmillion head of cattle out of 11 million in the country's herds, fear isrising that the same brain disease infecting the cattle may besurfacing in humans.
Bovine spongiform encephalitis (BSE) is the animal affliction thatled the European Union last week to demand the cattle be slaughteredto prevent BSE's spread across the English Channel to the continent.
Creutzfeldt-Jakob Disease (CJD) is the human prion infection, alsomarked by spongiform encephalopathy, that has struck down 10young British men and women since 1994. Only two of the 10 remainprecariously alive, with death inevitable.
These recent victims ranged in age from 16 to 39, which is whatalarms scientists and citizens in Britain. Until now, CJD has strickenonly the elderly, with a mean onset of 65 years, and a known lowerlimit of 39. Widespread in the world, such sporadic CJD has anincidence of one in a million.
Typically, neurologists see it first in CJD patients as a dementia withmyoclonus (muscle-jerks and twitches). This swiftly progresses toother symptoms of brain degeneration _ from mutism, ataxia andcortical blindness to behavioral changes and psychosis _ ending indeath within three to four months. Presumably, the infectionincubates sub rosa for five to 10 or more years before surfacingsymptomatically.
The pathogen responsible for this devastation is neither virus norfungus nor bacterium, but a prion _ which stands for proteinaceousinfectious agent. Neurologist Stanley Prusiner, of the University ofCalifornia, San Francisco, who discovered and named prions in 1982,described the oddball particles as "100 times smaller than thesmallest virus."
Besides CJD, Prusiner has inculpated prion proteins in fatal familialinsomnia, Gerstmann-Strassler syndrome, Alzheimer's andParkinson's diseases and kuru. (See BioWorld Today, Feb. 10, 1994,p. 1.)
Fatal kuru used to carry off members of the Fore tribe in NewGuinea, who ritualistically ate the brains of their ancestors andenemies. (See BioWorld Today, Nov. 17, 1994, p. 1.) Sheep have asimilar spongiform encephalopathy, called "scrapie" because prion-infected animals scrape and madly scrape their necks against treesand fence posts.
In 1989, a British report concluded that the source of BSE in cowswas cattle feed containing animal protein from sheep with scrapie.
Last Friday, the FDA said it would ban all protein from cud-chewinganimals in ruminant feeds.
In 1990, British authorities set up the National CJD Surveillance Unitto watch for signs that BSE was spreading to humans. Suddenemergence of the new youthful-onset variant of the disease among itsten recent victims suggests, but does not prove, that this is happening.
The Lancet, dated April 6, 1996, presents the Surveillance Unit's firstfindings. On 13 of the 66 pages in its current issue, the journalcarries: an editorial titled: "Less beef, more brain," followed by acommentary, "A dreadful challenge," an article, "A new variant ofCreutzfeld-Jakob disease in the UK," and a "Grand Round:Creutzfeld-Jakob disease in a young woman."
That patient, now 28 years old, is one of the two who have not yetsuccumbed to their disease. The Lancet reports describe the analysesthat she and eight others of the 10 underwent to seek some link to thebovine infection:
"One had worked as a butcher from 1985 to 1987 and another hadvisited an abattoir for two days in 1987. None had ever worked onfarms with livestock, although one patient had spent one week'sholiday a year on a dairy farm between 1976 and 1986. There was norecord of BSE in this herd. All nine cases were reported to have eatenbeef or beef products in the last 10 years, but none was reported tohave eaten brain. One of the cases had been a strict vegetarian since1991."
Brain autopsies and biopsies revealed that "the most striking andconsistent neuropathological abnormality in all cases was prionprotein plaques," extensively distributed throughout many regions ofthe brain. "This unusual feature," the report continued, "was not seenin any of the other 175 sporadic CJD cases investigated" since Mayof 1990, but resembled similar stigmata in the brains of sheep withscrapie.
Transgenic Mice Model Human Prion Gene
The jury is still out on accusing BSE of CJD. A verdict, as the reportindicates, "would require inoculation of human beings with BSE."
Short of that, transgenic mice expressing the human prion gene(located on chromosome 20) "offer an opportunity for exploringwhether bovine prions can induce production of human prionprotein."
So far, results of ongoing experiments with this animal model "arereassuring," the Lancet report states, and concludes: "The next stageof these studies is to challenge mice expressing only human prionprotein with BSE. This experiment is in progress, and so far suchmice remain well around 320 days post-challenge (mice of thisgenotype succumb to CJD in around 200 days). However, the end-point of this experiment may be 500-600 days away should thesemice not succumb to prion disease and die of old age."
Lancet's authors conclude: "Although the small number of cases inthis report cannot be regarded as proof, the observation of apotentially new form of CJD in the U.K. is consistent with such a link. . . We believe that [it] is a cause for great concern." n
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