Are there any vaccines against prion diseases

Creutzfeldt-Jakob disease: the latest case does not fit into the previous pattern

After a first case of Creutzfeldt-Jakob disease with heterozygous genetics has been confirmed, a wave of further diseases cannot be ruled out.

Photo: Science Photo Library / Equinox Graphics

More than 20 years after the appearance of the first diseases of the Creutzfeldt-Jakob variant vCJD in humans - as a result of bovine spongiform encephalopathy (BSE) in cattle (1) - British doctors have now detected a genetic variant in a deceased person that has not yet been found in the prion disease had been observed. A detail in codon 129 of his prion protein gene is unusual in this patient: normally this codon can code for the amino acids methionine (M) or valine (V). Humans can thus be homozygous (MM, VV) or heterozygous (MV) with regard to this trait. Up to now, however, vCJD had only been diagnosed in patients with the homozygous MM type. In Great Britain 1 patient has now died who has the heterozygous form of the prion protein gene (MV type) for the first time (2). It is assumed that in the normal population
37% are homozygous for methionine (MM), 12% are homozygous for valine (VV) and 51% are heterozygous for methionine and valine (MV).

The deceased 36-year-old man was admitted to the National Center for Prion Diseases in London in August 2015 with severe personality changes, memory disorders, gait ataxia and myoclonus. 25 points in the mini mental status test showed slight dementia. Neurologically, there were pyramidal, extrapyramidal, extraocular and cerebellar signs. Diffusion tensor imaging (DTI) revealed abnormalities in the basal ganglia, hypothalamus, medial thalamus and the insula. The man's condition worsened and he died in February 2016.

There are two similar case reports in the literature

It was previously unknown whether people with heterozygous genetic makeup for the prion protein are immune to vCJD or whether they only become ill after a longer incubation period (around 35 years after infection). Although there are two similar case reports in the specialist literature, vCJD could not be diagnosed with certainty (3, 4). However, there are parallels to the prion disease Kuru, the iatrogenic form of CJD, which initially only affected people with two identical genes, but later also those with mixed genes.

What makes the now published case of vCJD so special? “Up until now, there was a possibility that 60% of the population with MV or VV equipment could be immune to vCJD. This is obviously not the case, "says Prof. Dr. med. Walter Schulz-Schaeffer, Director of the Institute for Neuropathology, Saarland University Hospital.

“This makes another explanation more likely, according to which the genotype MV extends the incubation time between the ingestion of infectious material and the onset of the disease. This could mean that after the first wave of vCJD due to MM has subsided, further diseases will follow with a delay, affecting MV patients. ”According to Schulz-Schaeffer, the MV patient who died in 2016 could have ingested the pathogen as a child - and have lived with it for almost thirty years without any problems.

The current case is held by Prof. Dr. Inga Zerr, Head of the National Reference Center for the Surveillance of Transmissible Spongiform Encephalopathies and Head of the Prions Research Group, University Medical Center Göttingen, for scientifically and health-politically relevant: “The occurrence of a disease in heterozygotes had been feared for many years and was never completely ruled out. It can be assumed that further diseases are to be expected. ”However, the number of cases could not be reliably estimated because too many unknown factors are included in the calculation.

Priv.-Doz. Dr. Michael Beekes, head of the Prions and Prionoids Research Group at the Robert Koch Institute (RKI), sees another potential risk: "In addition to the brain and spinal cord, other parts of the body and the blood of subclinically infected people can also contain vCJD pathogens." to rule out that the vCJD pathogen could be transmitted during medical measures - through blood and blood products, transplants or surgical instruments.

"So far, 4 cases of probable vCJD transmission by blood in the transfusion recipient and one case of suspected infection by a plasma preparation have been reported in the UK," said Beekes. Three of the transfusion recipients in question were also clinically ill with vCJD. However, Beekes emphasizes that there is no evidence that there is a risk of vCJD transmission through normal social / nursing contacts or through the air.

Strict conditions are intended to prevent transmission

“The safety of surgical instruments, grafts, and blood and blood products has received a great deal of attention with regard to vCJD for many years. Against the background that there are currently no practicable test procedures for the general examination of blood donors or blood donations for vCJD pathogens, people in Germany who stayed in the UK for more than 6 months between 1980 and 1996 are excluded from donating blood . "

In addition, when reprocessing surgical instruments, at least 2 suitable procedures should always be combined. This includes cleaning in an alkaline environment and subsequent steam sterilization at 134 ° C (5). In the opinion of the prion researchers, if these measures are observed, vCJD cannot be expected to spread in Germany. But this looks much more critical for other European countries.

Regardless of this, around 100–130 people will continue to develop the sporadic Creutzfeldt-Jakob disease (sCJD) every year. Most patients are 60–70 years old. According to Schulz-Schaeffer, the pathological changes in the brain and body of the recently deceased vCJD patient differ from those with sCJD a wreath around the outside are the vacuoles - and evidence of prion deposits in the lymphatic tissue, ”says Schulz-Schaeffer.

To get an impression of how widespread this finding is in the population, British researchers (6) have carried out an epidemiological study. Based on the examination of 32,441 appendix biopsies, they have calculated that statistically every 2,000th Briton born between 1941 and 1985 has a pathological prion protein in the lymphatic tissue.

As far as we know today, these are the people who do not necessarily have to become ill themselves, but who could incubate a vCJD. In this way, the prion protein could get to more susceptible people. From animal experiments it is known, for example, that the lymphatic deposition of the prion protein precedes the brain disease.

“Among the people whose lymph tissue tested positive there were also people with MV and VV polymorphisms at codon 129 of the prion protein gene,” says Schulz-Schaeffer. “So far, it was not known whether people other than the 40% MM carriers at prion codon 129 in the population could develop BSE-associated vCJD and what the clinical picture could look like in these people.

The current work indicates that the clinical picture of a number of people - who have not yet been classified as vCJD-susceptible - may be more similar to sporadic diseases (sCJD) than that of the vCJD observed so far, while the damage pattern in the brain can be assigned to BSE-associated vCJD let.

The development of diagnostic procedures is a priority

“Since the effective interruption of the chain of infection in the cattle reservoir and because of the strict testing of animals for human consumption, no relevant new entry of the BSE pathogen into the food chain is to be expected. The actual risk is that which has been adapted to humans and is therefore many times more dangerous in terms of spreading in unrecognized vCJD carriers, ”says Schulz-Schaeffer.

In the opinion of the prion researcher Zerr, there is a need for research in view of the current publication in order to further clarify the risks posed by the new form of vCJD. For this reason, special emphasis must be placed on the development of diagnostic methods that indicate the infectiousness or the disease early enough and that can be used as a screening method.

Dr. med. Vera Zylka-Menhorn

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