Prion disease: why Russia is not diagnosed, deadly proteins in meat and lack of treatment

With the advent of the Internet and free media, people began to learn more and more about deadly diseases -

infectious, viral, oncological andhereditary. But few have heard of fatal prion diseases. Despite clinical trials, there is currently no proven universal treatment for this group of diseases. Neuroscientist Richard Johnson of Johns Hopkins University says that if a patient's prions have turned pathological, they die, and we can't avoid that.

What is prion disease

Prion diseases - they are also calledTransmissible spongiform encephalopathies are a family of rare, progressive neurodegenerative diseases that affect both humans and animals. They are distinguished by:

  • long incubation period;
  • characteristic spongy loosening of brain tissue associated with the loss of neurons;
  • the inability of the immune system to respond to infection by initiating an inflammatory process.

Prion diseases affect both humans and animals, progress rapidly and always lead to death.

Prions in the macro

The causative agent of the disease is prions, a type of protein withabnormal tertiary structure, not containing nucleic acids. The term itself refers to pathological pathogenic agents that are capable of causing abnormal folding of specific normal cellular proteins, which are called prion proteins, found most often in the brain. The functions of these normal prion proteins are still not fully understood.

Creutzfeldt-Jakob disease— CJD, spastic pseudosclerosis, corticostriospinal degeneration syndrome, transmissible spongiform encephalopathy, mad cow disease.
This is a progressive degenerative diseasecerebral cortex, basal ganglia and spinal cord. It is considered the main manifestation of spongiform encephalopathy (prion disease). There is no cure. CJD affects people of all nationalities and races, men and women, adults and children.

Prion proteins- normal proteins that are present ineach person. But there are certain groups of people who have a genetic mutation that predisposes them to the synthesis of pathogenic prion protein. Prion diseases can also be transmitted through direct infection, transmission can also occur during surgery, the use of human growth hormone, or the consumption of contaminated meat. This type of infection is called iatrogenic and it remains in the minority compared to other forms of CJD.

Percentage of iatrogenic cases of Creutzfeldt–Jakob disease in the National CJD Research & Surveillance Unit in 177 patients.

  • Growth hormone (somatotropin) - 53.1% (94 cases).
  • Dura mater (including eating) - 38.9% (69 cases).
  • Gonadotropic hormone - 2.25% (4 cases).
  • Neurosurgical instrumentation - 2.25% (4 cases).
  • Corneal transplantation - 1.69% (3 cases).
  • Electrodes for stereoelectroencephalography - 1.12% (2 cases).
  • Liver transplantation - 0.56% (1 case).

There are cases of infection that are notclassified for any of the two above-mentioned reasons, in which case they are considered sporadic, that is, they have arisen spontaneously and independently, due to circumstances independent of genetics or external factors.

Dr. Oybek Turgunhuzhaev, Headdirections for neurorehabilitation at the Interdisciplinary Rehabilitation Center (Moscow), says that the final diagnosis of a person with suspected any prion disease is based on an assessment of clinical signs and symptoms and a number of supporting studies. For a long time, the only method for confirming the diagnosis was electroencephalography. But since the overall sensitivity of this method is limited, the usefulness of this study was questioned.

Why in Russia do not put this diagnosis

Prion diseases are incurable, they are inevitablefatal. In addition, the problem is that to make a reliable diagnosis it is necessary to perform an autopsy. Any autopsy is a risk for the pathologist, as there have been cases of iatrogenic infection of specialists from deceased patients.

By order of Rospotrebnadzor, that a personill with prion disease must be notified within two hours. At the same time, the establishment of such a diagnosis leads, according to Russian instructions, the disposal of all equipment with which the patient was in contact. That is why, when Medusa told the case of one of the patients with CJD, all the clinics said that they did not have the equipment to observe such patients. In fact, it’s just a way not to lose millions of rubles, even scrapping an MRI machine. If it were about hundreds of diagnoses of a prion disease (for example, in the USA 300 cases are registered annually, possibly more), then it would be about losing billions of rubles for Russian hospitals and the budget. That is why the diagnosis is not officially made, doctors do not want to talk about it, since there is no official order that a diagnosis cannot be made. As a result, it turns out that there is a disease, there is death, and there are no reasons for relatives and dying people.

Nobody will tell them that most likely relativesalready infected. No one will say that you can not try raw minced meat or eat raw meat, especially brains. Also, because a diagnosis is not made, it is possible to accidentally transplant the organ of a patient with a prion's disease, thereby infecting another person. It can also occur through a surgical instrument (there were such cases, more on this below).

When we asked at least someone to tell us aboutprion diseases, almost no one was ready to speak openly. So we anonymously talked with a neurologist at one of the largest Moscow hospitals. “There are two problems with prions. Firstly, to make a reliable diagnosis it is necessary to perform an autopsy. Although formally (according to Russian guidelines, for example), an autopsy can be performed, albeit under special conditions. Any autopsy is naturally an additional risk for pathologists, because cases of pathologists becoming infected from deceased patients have been described. no one wants to transfer the risk to them.

Secondly, since prion infections are hardflowing, incurable diseases (albeit with a rather complicated mode of transmission), in our country are pretty darn complicated laws for registering and managing such patients; cases must be reported in case of detection within almost two hours, after diagnosis, it is necessary to carry out the destruction of part of expensive equipment, which, as it may turn out, did not even lie next to the patient, reissue documents and so on.

Pretty sad, but nonetheless truthful, the fact is that the correct diagnosis does not matter to the patient. There is still no cure. ”

Creutzfeldt-Jakob disease

Creutzfeldt–Jakob disease (CJD) is oneof the types of prion diseases. It is a rapidly progressive, fatal neurodegenerative disease that is believed to be caused by an abnormal isoform of the prion protein. CJD occurs worldwide and statistics estimate that 1 in a million people are affected worldwide.

Prion diseases do not go the same way.scenario, people suffering from the same prion lesion may differ epidemiology and pathogenesis. Creutzfeldt-Jakob disease is divided into several types.

Sporadic form - sore from mutation, coughing, experiencing headache and memory lapses

Sporadic Creutzfeldt-Jakob Disease (SCAN) -the most common type of transmissible spongiform encephalopathy in humans, which accounts for about 85% of cases of registered diseases of prion nature. SBCYA has a very rapid course of the disease - the average life expectancy after the onset of symptoms is only six months. More than 90% of patients die within a year after the onset of symptoms. The peak incidence occurs in older people 60–70 years of age, in other age groups it happens much less frequently. One of the hypotheses of the origin of SCDM is the opinion that this is a spontaneous neurodegenerative disease resulting from a somatic mutation of the PRNP gene or an accidental structural change in the PrP protein, causing the formation of PrPSc2. Epidemiological studies did not reveal a connection between the sporadic form of CJD and environmental factors.

Snapshot mrt patient CJD

The first symptoms of SCAD are usually non-specific: headache, malaise, cough, dizziness, and changes in behavior, mood, or memory lapses. To confirm the diagnosis, time must pass in order for other reasons to appear to suggest prion nature. The classic clinical signs with CJD are:

  • rapid decline in cognitive abilities;
  • ataxia (violation of the coordination of the movement of various muscles);
  • myoclonus (rapid sudden contractions of individual muscles), ending in akinetic mutism (inhibition of all motor functions, except for the fixing movements of the eyeballs).

The final diagnosis depends on evaluation of clinical manifestations and laboratory test results.

Akinetic Mutism- a condition in which patients stopmove and follow the target with the eyes, with the exception of the reaction of the eyes to stimuli or prolonged fixation of gaze, their muscles periodically contract rapidly on their own or under the influence of external factors. Patients suffer from incontinence and make no sounds or only inarticulate noises. If swallowing persists, patients can live in this condition for several weeks, even years with other favorable factors, receiving nutrition intravenously or through a tube. In the sporadic form of CJD, patients reach this state during the first weeks of the disease. In the fastest scenarios, 10% of patients reach this state within a year.

For a long time the most informative waydiagnosis was performed by diffusion-tensor MRI. This method is the most accessible, relatively non-invasive and effective for early changes in the cerebral cortex. SBKYa can be detected through markers in nasal mucous membranes, cerebrospinal fluid, urine or blood, but these tests often give false positive results - protein 14.3.3 is not specific without the appearance of a concomitant clinical picture. The proteinogram is a new optimal method for diagnosing SCD, as it is the most sensitive of all of the above.

Proteins 14-3-3- a family of regulatory molecules foundin all eukaryotes. They bind to a variety of other proteins, regulating their functions and thereby influencing many processes, including cell cycle regulation, metabolic control, apoptosis, and control of gene transcription. They were discovered more than 40 years ago during the systematic classification of proteins in nervous tissue, where their content exceeds 1% of all proteins. To date, more than 300 different target proteins capable of interacting with 14-3-3 have been described.

Proteinogram- a study that studies the quantitative relationship of protein varieties in the blood. The concept of total protein includes all possible proteins, despite their differences in structure and function.

Hereditary form of Creutzfeldt-Jakob diseaseand fatal familial insomnia associated with genetic mutations, constitute only 10% of all cases of prion diseases. Many studies indicate that the general pathway in the pathogenesis of a disease can be common for both sporadic and hereditary forms of prion disease, except that in the first case, protein transformation occurs without the participation of any factors, and is not predetermined by the presence of mutation in the genes.

(A) Sponge-like degeneration in the cortex of largehemispheres. Inset: neurons containing vacuoles. (B) The cerebellum bark with kuru plaques (PAS reaction), which consist of PrPsc aggregates. (B) Plaques in the cortical substance, surrounded by a spongy-shaped degeneration zone, with a new variant of Creutzfeldt-Jakob disease.

Studies of hereditary forms of CJD and fatalfamily insomnia provided scientists with the opportunity to study the course of phenotypic heterogeneity (a variety of “strains”) of prion disease. Although many other neurodegenerative diseases, such as Alzheimer's disease, amyotrophic lateral sclerosis and Huntington's chorea, are quite similar in phenotype, prion disease includes many clinically different symptoms.

Phenotype- a set of characteristics inherent at a certain stage of disease development. The phenotype is formed on the basis of the genotype.

Polymorphism- the ability of some organisms to exist in states with different internal structures or in different external forms.

With hereditary prion disease, phenotypediseases will be determined by the combined effect of pathogenic mutations, codon 129 polymorphism and PrP Sc type. Codon 129 polymorphism plays a dual role in predicting the outcome of a disease. Central to the understanding of the pathogenesis of prion disease is a detailed and accurate knowledge of the processes and conditions in vivo for the formation of PrPSc, which inevitably leads to the development and expression of the disease. This knowledge will allow you to develop a rational and effective strategy for therapeutic intervention.

New variant of CJD - to get infected by eating a piece of meat

New variant of Creutzfeldt–Jakob disease(nvCJD) was first identified in 1996. Subsequent studies supported the hypothesis that this form is associated with bovine spongiform encephalopathy. Most likely, the patients ate meat containing pathological cow brain prions.

Unlike the sporadic form, the disease does not have a clear age of infection.Patients with nCJD often have psychiatric symptoms and are sometimes misdiagnosed as a psychiatric disorder rather than a neurological disorder.The true cause of psychiatric symptoms lies in cognitive impairment, persistent pain in the limbs, sensory impairments (paresthesia or dysesthesia), speech or vision disorders.

Within 6 to 8 months, malformations of the muscular system develop, but in some cases, the development of the disease canTherefore, this diagnosis is quite difficult to make at the first signs of the disease.If the patient has uncontrollable movements, the likelihood of a competent diagnosis of nCJD increases.In contrast to the sporadic form, which is characterized by sudden muscle spasms under tension (myoclonus), in the case of the new form, dystonia (a syndrome in which there is apersistent spasmodic muscle contraction), and chorea (a syndrome characterized by erratic, jerky, irregular movements).

The lethal stage of the new form is similar to the lethal stage of the sporadic form of Creutzfeldt-Jakob disease, it passeswith progressive loss of muscle control, often leading to a state of akinetic mutism.

Dementia and CJD: someone is sick and does not even know about it

Unlike the more common dementia conditions, which usually take years to develop, rapidly progressive dementias candevelop over months, weeks, or even days and lead to death.The sporadic form of CJD accounts for 46.9% of all reported cases of rapidly progressive dementia, and the genetic form of prion diseases accounts for 13.6%.39% of all cases are frontotemporal dementia (FTD), corticobasal degeneration (CBD), Alzheimer's disease (AD), Lewy body dementia (DLB), and progressive paralysis.

Typically, the sporadic form of CJD presents with a combination of dementia and neurodegenerative or psychiatric symptoms.Pyramidal, cerebellar and focal cortical dysfunction are common in such patients.In one-third of patients, dementia is preceded by complaints of fatigue, headache, sleep disturbance, malaise, weight loss, pain, depression or changes in behavior.

Neurological symptoms including ataxia, dysesthesia, dementia, or muscle disorders (chorea, myoclonus, or dystonia) appear later.Most cases of rapidly progressive dementia without other accompanying symptoms occur in older adults due to metabolic disorders or acute infections (pneumonia or urinary tract infections).Therefore, before undergoing laboratory tests, doctors primarily indicate rapidly progressive dementia without a clear diagnosis.The final verdict depends onThe results of the tests and examinations obtained, the diseases will differ depending on theAn EEG can help rule out seizure activity in the brain and address the diagnosis of other conditions, such as CJD.

Rapidly progressive dementia presentone of the most difficult neurological problems. Differential diagnosis is widely used to confirm definitive diagnoses that may relate to neurodegenerative, autoimmune, infectious, and neoplastic diseases. Even with such a careful approach to the examination of patients, a small percentage of cases are diagnosed after death.

Fatal familial insomnia

Fatal familial insomnia is a rare prion disorder that literally deprivessleep and leads to a decrease in all neuro-motor and mental functions.Two forms of this disease can be distinguished: genetic and sporadic.

The genetic form is associated with a mutation that results in the conversion of the PrP protein into a prion protein.Sporadic disease, on the other hand, appears spontaneously, without any prerequisites.Other prion diseases are affected by the area of injury – the conversion of prion proteins into pathological ones predominantly occursin one part of the brain, the thalamus, which, among other things, is responsible forand for sleep.

Average age of onset of symptomsgenetic form of fatal familial insomnia - 40 years. Early symptoms include minor difficulty falling and staying asleep, muscle twitching, cramps and numbness. During sleep, people may sleep restlessly: move their legs and arms, toss and turn. Eventually, patients stop sleeping. Because of this, mental activity decreases and muscle coordination is lost (ataxia). Patients experience increased blood pressure, increased heart rate and excessive sweating. Unlike other prion diseases, there is no spongiform degeneration of the brain substance in fatal familial insomnia. The main signs of damage are neuronal degeneration and reactive gliosis (formation of “scars” on and in brain tissue) in the nuclei of the thalamus, as well as neuronal degeneration in the complex of medulla oblongata nuclei.

Brain Sick with Fatal Family Insomnia

A diagnosis of fatal familial insomnia in a genetic form is confirmed by genetic testing.In the case of sporadic cases, abnormalities in sleep patterns and abnormalities in the thalamus can be detected by polysomnography and positron emission tomography (PET).The average life expectancy from the onset of the first symptoms of the disease is 3 years, and there is no cure.

Slow progressing dementia: symptoms over several years

Gerstmann-Straussler-Scheinker syndrome isa rare genetic form of transmissible spongiform encephalopathy, which was first described by Austrian neurologists in 1936. The syndrome most often appears between the ages of 40 and 50 and is caused by mutations in the PRNP prion protein genes on chromosome 20.

The clinical picture of the syndrome is similar tosporadic form of CJD, but it differs in duration and slowly progressive dementia, along with other symptoms. Gerstmann-Straussler-Sheinker syndrome can last for several months or several years, the average life expectancy is 5 years. It is possible to diagnose the disease even in the early stages through magnetic resonance imaging. MRI will show spongy changes in the cortex and proliferation of glial cells.

Glial cells or neuroglia- a collection of auxiliary cells of the nervous tissue. Makes up about 40% of the volume of the central nervous system. The number of glial cells in the brain is approximately equal to the number of neurons.

Glial cells have common functions and, in part,origin (exception - microglia). They constitute a specific microenvironment for neurons, providing conditions for the generation and transmission of nerve impulses, as well as carrying out part of the metabolic processes of the neuron itself.

Detecting prion disease is enoughlabor-intensive, given that if the diagnosis is confirmed, the patient is no longer able to help, and hospitals lose millions of rubles. And the worst thing is that all people on Earth are at risk. Prions will not spare anyone. Therefore, do not try the stuffing after it has been salted. Do not eat the guts and brains of cows and pigs, and visit the doctor on time. In the end, an MRI will not lie.