Mad cow disease: fatal Creutzfeldt-Jakob disease
A few years ago it was said that the so-called "mad cow disease" (BSE) in Europe was almost defeated. However, Creutzfeldt-Jakob disease (CJD), which is most likely caused by the consumption of beef contaminated with BSE, appears to remain dangerous. The causative agent of the fatal disease is still common.
Creutzfeldt-Jakob disease is always fatal At the beginning of the decade it was reported that experts assume that the so-called "mad cow disease" (BSE, bovine spongiform encephalopathy) in Europe was almost defeated. But the human form of mad cow disease, Creutzfeldt-Jakob disease, remains obviously dangerous. The so-called new variant of the disease (vCJD) is distinguished from the accidentally (sporadically) occurring Creutzfeldt-Jakob disease. In the vCJD, depressive mood, anxiety, delusions and hallucinations usually occur initially. In the later course, there are severe movement disorders and a loss of mental performance (dementia). Both the sporadic and the new variant of the brain disease is always fatal. In a current article, the "world" is dedicated to the topic.
BSE can be transmitted to humans About two decades ago, it was shown that BSE, the disease that eats cows' brains, is transferable to humans. The first young women and men developed symptoms of the new plague. The first scientific contributions to the so-called vCJD followed in 1995. "It was not surprising for experts that BSE can be transmitted," explained Professor Inga Zerr from the University of Göttingen according to the "Welt". "But nobody thought that those affected would be much younger than CJK patients before." The two patients, whom British neurologists reported in the specialist magazine "Lancet" at the time, were 16 and 18 years old. The youngest patient to date was reported to be twelve years old when the disease started. People with vCJD die on average before their 30th birthday. "However, the range of fluctuation is large," says Zerr.
Hope for the end of the wave of diseases A total of 229 cases of the new variant were registered at the surveillance center for CJD in Edinburgh by June 2014, of which 177 from Great Britain. "So far, not a single case has become known in Germany," explained Zerr. Since the peak in 2000, the numbers have dropped and there was hope for the end of the wave of diseases. However, Professor Armin Giese from the Ludwig Maximilians University in Munich warns: "Calmness can be deceptive." According to the article, half of the population could still face a wave of vCJD diseases. "This is a very realistic scenario," says Zerr. However, the risk is purely theoretical. So far there are no direct indications. "It can also happen that nothing happens," says the neurologist. "And this possibility becomes more and more likely from year to year."
Incorrectly folded protein molecule responsible for disease Creutzfeldt-Jakob is caused by an incorrectly folded small protein molecule, a so-called prion. If misshaped prions reach the brain, for example after eating BSE-contaminated beef, this can have fatal consequences. As the "Welt" writes, in a kind of domino effect, the body's proteins fold into the wrong fold, which in turn causes the brain tissue to degenerate and spongy, perforated structures arise. Position 129 of the prion composed of amino acids is decisive for one's own risk of disease. So far, only people with two genes for the amino acid methionine got sick at this point. 40 percent of the population have such a double methionine gene. Nothing is known about the vCJK risk of the ten percent who wrote double building instructions for the amino acid valine in their genome. For the remaining 50 percent, who each have a plant for methionine and one for valine, there are gloomy indications.
Hormones from the pituitary gland of corpses It was the case with the Kuru prion disease that people with two identical genes first fell ill and later those with mixed genes. Because it was common for the affected people in Papua New Guinea to eat the meat of deceased tribesmen, misfolded prions continued to spread and more and more people died until cannibalism was banned in 1954. A similar difference had been shown in the CJK diseases of people who received growth hormones from the corpus pituitary gland in the 1960s to 1990s. In both cases, the incubation period was twice as long on average for those with mixed genes than for those with two identical genes. Most people at vCJD assume that the methionine / methionine population is around ten to 15 years old. "But that's only an estimate, based on the maximum BSE," says Zerr, "you never know when the individual was infected." For half the population, the incubation period could be 20 to 30 years. "But that's just statistical gimmicks."
Security in 20 years time However, many people wear incorrectly folded prions without suffering from vCJD. "After the first few cases, the United Kingdom specifically checked: How high is the infection rate of the population?" Says Giese. The examination of thousands of tissue samples from tonsils and appendix removed during surgery showed that "on average, one in every 2000 people is a carrier of incorrectly folded prions". However, as the prion researcher explained, the result does not mean that the disease will still break out in all these people. "It may be that the amount in the body remains low and they never get sick." Even if it is clear that with the many carriers there is a risk of transmitting sick prions via surgical equipment or with blood donations, there are so far in the database only three vCJD deaths due to blood donations were recorded in Edinburgh. "At worst, the disease can become endemic," says Zerr. In the best case, nothing happens. "It will only be possible to say in 20 years: Everything went well."
No therapy and no approved blood test Irrespective of this, 100 to 130 people will continue to develop Creutzfeldt-Jakob disease every year. The majority of patients are 60 to 70 years old. "Only three to six people a year are younger than 50," explained Zerr. There is no therapy for the disease and no approved blood test for diagnosis. "This is not interesting for the large pharmaceutical companies because of the small number of cases," says Zerr. Symptoms such as headache, memory disorders, hallucinations, personality changes, paralysis and dementia initially appear in the sick. In the further course, the disease leads to more and more errors and finally the complete failure of all brain functions. Affected people remain in the final stage, which can last for a long time, in a kind of rigidity without the possibility of contacting the environment. "What remains is a breathing and metabolic envelope with a pumping heart," says Giese.
Disease slowed down in animal experiments The sporadic CJD leads on average to death within six months, the other variant in a period twice as long. Even if there are no clear differences in the symptoms, a reliable distinction is still possible. "With vCJD there are vesicular changes with typical deposits in the brain," explained Zerr. But this can only be checked after death. "During life, certain changes in the thalamus can be recognized as a bright signal in nuclear spin." A blood test for CJK already works as a test approach, but there are still too many positive results, that is, an attack without a pathogen. Research continues even after therapy. According to Giese, the active ingredient "anle138b", which intervenes in the refolding process, is a beacon of hope. At least in animal experiments, the disease was slowed down. Clinical studies with the first patients are scheduled to begin next year. All previous therapeutic approaches have in common that they are only useful if the intervention is very early. "Nerve cells that are lost remain lost," said Giese. Zerr added that an interesting and important “side finding” of CJK research is that similar brain processes also play a role in Parkinson's and Alzheimer's disease. "We would not have recognized this without intensive prion research." (Ad)
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