Mad cow disease

1996/11/01 Alvarez, Mikel | Umaran Sanchez, Adelaida Iturria: Elhuyar aldizkaria

• Osasuna

Spongiform encephalopathies in animals

The model of these spongiform encephalopathies is sheep scrapie. After three years of incubation, the nervous system deteriorates and without solution, the animal dies after suffering paralysis. How is it transmitted? At the moment, little is known about the means of transmission and, in order to clarify it, the disease has been artificially transmitted to rats.

In 1987, a disease very similar to scrapie attacked cattle in Britain. The disease has become popular worldwide under the name of ‘mad cow disease’, when it was thought that feed made with scrapie infected sheep bones could have something to do and since then more than 100,000 cases have been reported. Although since 1988 the use of this feed is prohibited, this disease affects numerous groups of cattle in Britain and around the world.

Spongiform encephalopathies in man

Not only in animals, but also in humans there have been spongiform encephalopathies with similar clinical and histopathological characteristics. Based on epidemiological characteristics, these encephalopathies are known by different names: Creutzfeldt Jakobs syndrome, fatal family or Gerstmann-Straussler insomnia.

Although the names are different, these diseases have the same characteristics; the incubation is long, from 15 months to 30 years, after which, without inflammation or immune signals, the nervous system deteriorates. The basic lesion is the vacuolation of neurons and finally the brain becomes spongiform. At the moment no effective treatment is known and 9 to 18 months after the first symptoms the patient dies. These first symptoms are similar in diseases known by different names: visual alterations, mobility problems and dementia.

Kuru

Although some researchers have confirmed that these encephalopathies are transmitted through contaminated meat, the total test has not yet been obtained.

The disease known as Kuru was described in 1957 and was first known in a tribe of New Guinea, dedicated to the rites of cannibalism, mainly among children and women. Among the rites described, the most striking is the consumption of brains of dead relatives, which as soon as it was “discarded” the custom disappeared. Researcher Gadjus showed that the puncture or inoculation of brain samples from the dead to a chimpanzee inside the brain caused the transmission of the disease. In the same investigation, Gadjus tried to isolate the causal agent, since the agents that were isolated in contaminated curves and those affected by Creutzfeldt-Jakobs syndrome were very similar.

Creutzfeldt-Jakobs disease

We have said before that the area of influence of the Kuru was very well delimited. The case of Creutzfeldt Jakobs disease is very different; occasionally it attacks the general population and sometimes appears in apparently disconnected groups, although in all cases the presence is relatively low (one case per million each year). Cases are more common among people over 60 years of age. It has been shown that the puncture of brain samples of deceased cats and monkeys causes the disease of animals.

Moreover, the possible horizontal transmission among humans has been observed, among others, in corneal transplants, duramadre vaccines and treatments with growth hormones obtained from the bodies.

Although this has been demonstrated, exceptions have also been found. For example, the incidence of CJD among Libyan Jews is very high, 100 times higher than normal and is also concentrated in families. This leads us to think in advance that there is a certain genetic tendency, since in these groups the effect of fatal family insomnia or Gerstman-Straussler disease is also very important.

Etiology of Spongiform Encephalopathies

Therefore, in some spongiform encephalopathies it can be said that hereditary genetic characteristics are important. However, it has been shown that diseases can be transmitted, but the agent responsible for transmission is not yet known. According to the data we have so far, this agent is not a bacterium and, although some researchers believe otherwise, it has not been shown to be a virus. What we know is that the substance that transmits these diseases is the protein called prion. The prion has the capacity of self-replication and, as it were, in prose, we can affirm that it violates all the laws of biology.

So far, the only known molecules with self-replication capability were nucleic acids, so researchers have certainly searched for particles that transmit DNA and RNA, but so far this effort has been useless. These particles exceed nuclease treatments and manage to maintain themselves. So things, besides saying that prion is a great contagious agent, it must be recognized that it is one of the most interesting discoveries of biology for years.

Prions

Prions are 33-25 kDa oligomers. Other proteins in neuronal membranes are very similar, but with a small change, their resistance is enormous. On the one hand, they are able to cope with proteolysis, which facilitates their integration into neurons. On the other hand, the transmission lines are very wide and effective: the work equipment is not disinfected by OM radiation, boiling, formaldehyde, etc.

In most cases of CJD known so far, this change has not occurred in a sequence of amino acids, but in the change of adaptation after translation. That is, the prion appears as an isomer of the normal protein, so it is logical to think that it is only a curious phenomenon as the mutation that occurs in certain human beings.

In this sense, several hypotheses have been formulated, one of which considers that the transformed protein forms a heterodimer with the normal protein molecule and that later the normal protein becomes a prion. These two transformed proteins will look for two other normal proteins to form the heterodimer and eventually develop into an autocatalytic and exponential process. The main result of the process is the accumulation of abnormal proteins resistant to digestion, which is the beginning of neurodegeneration.

A mutation in codon 102 of the gene encoding normal protein has been identified in family syndromes. It is expressed as autosomal dominant and increases the production possibilities of modified prion protein, also facilitating the formation of heterodimers.

Transmission of spongiform encephalopathies

Since these prions accumulate slowly, there are many issues that can be posed from an epidemiological point of view. The first symptoms occur months or years after eating contaminated meat, so it is very difficult to determine how the disease has been reached. Although some researchers have confirmed that these encephalopathies are transmitted through contaminated meat, for the moment the complete test has not been obtained, so it can be said that there is no epidemiological relationship between mad cow disease and CJD that occurs in humans. On the other hand, incubation time is so long that, despite being infected by prions, it can cause death. That is why, according to alarmists, this epidemic could be a public health problem.