Creutzfeldt-Jakob disease
Encyclopedia
Creutzfeldt–Jakob disease or CJD is a degenerative
neurological disorder
(brain
disease
) that is incurable and invariably fatal. CJD is at times called a human form of mad cow disease
, given that bovine spongiform encephalopathy
is believed to be the cause of variant Creutzfeldt–Jakob disease in humans.
CJD is the most common among the types of transmissible spongiform encephalopathy
found in humans. In CJD, the brain tissue develops holes and takes on a sponge-like texture. This is due to a type of infectious protein called a prion
. Prions are misfolded
proteins which replicate by converting their properly folded counterparts.
of CJD is rapidly progressive dementia
, leading to memory
loss, personality
changes and hallucinations. This is accompanied by physical problems such as speech impairment, jerky movements (myoclonus
), balance and coordination dysfunction (ataxia
), changes in gait
, rigid posture
, and seizures. The duration of the disease varies greatly, but sporadic (non-inherited) CJD can be fatal within months or even weeks (Johnson, 1998). In some people, the symptoms can continue for years. In most patients, these symptoms are followed by involuntary movements
and the appearance of an atypical diagnostic electroencephalogram tracing. Most victims die 6 months after initial symptoms appear, often of pneumonia due to impaired coughing reflexes. About 15% of patients survive 2 or more years.
The symptoms of CJD are caused by the progressive death of the brain's nerve cells
, which is associated with the build-up of abnormal prion
proteins forming amyloids. When brain tissue from a CJD patient is examined under a microscope
, many tiny holes can be seen where whole areas of nerve cells have died. The word "spongiform" in "transmissible spongiform encephalopathies" refers to the sponge-like appearance of the brain tissue.
s. The diseases are thus sometimes called prion diseases. Other prion diseases include Gerstmann–Sträussler–Scheinker syndrome (GSS), fatal familial insomnia
(FFI) and kuru
in humans, as well as bovine spongiform encephalopathy
(BSE, commonly known as mad cow disease) in cattle, chronic wasting disease
(CWD) in elk and deer, and scrapie
in sheep. Alpers' syndrome in infants is also thought to be a transmissible spongiform encephalopathy caused by a prion.
The prion that is believed to cause Creutzfeldt–Jakob exhibits at least two stable conformations. One, the native state, is water-soluble and present in healthy cells. , its biological function is presumably in transmembrane transport or signaling. The other conformational state is relatively water-insoluble and readily forms protein aggregates.
People can also acquire CJD genetically through a mutation of the gene that codes for the prion protein (PRNP).
This occurs in only 5–10% of all CJD cases.
The CJD prion is dangerous because it promotes refolding
of native proteins into the diseased state. The number of misfolded protein molecules will increase exponentially
and the process leads to a large quantity of insoluble protein in affected cells
. This mass of misfolded proteins disrupts cell function and causes cell death. Mutations in the gene for the prion protein can cause a misfolding of the dominantly alpha helical regions into beta pleated sheets. This change in conformation disables the ability of the protein to undergo digestion. Once the prion is transmitted, the defective proteins invade the brain and are produced in a self-sustaining feedback loop.
Stanley B. Prusiner
of the University of California, San Francisco (UCSF) was awarded the Nobel Prize in physiology or medicine
in 1997 for his discovery of prions. For more than a decade, Yale University
neuropathologist Laura Manuelidis
has been challenging this explanation for the disease. In January 2007, she and her colleagues published an article in the Proceedings of the National Academy of Science and reported that they have found a virus
-like particle (but without finding nucleic acid
s so far) in less than 10% of the cells a scrapie-infected cell line and in a mouse cell line infected by a human CJD agent.
l grafts, dural grafts or electrode
implants (acquired or iatrogenic
form: iCJD); it can be inherited (hereditary or familial form: fCJD); or it may appear for the first time in the patient (sporadic form: sCJD). In the hereditary form, a mutation
occurs in the gene
for PrP, PRNP
. Ten to 15 percent of CJD cases are inherited. (CDC)
The disease has also been shown to result from use of Human Growth Hormone obtained from the pituitary gland
s of persons who died from Creutzfeldt–Jakob Disease, though the known incidence of this cause is (as of April 2004) quite small. The risk of infection via cadaveric HGH in the US ceased when the medication was withdrawn in 1985.
It is thought that humans can contract the disease by consuming material from animals infected with the bovine form of the disease. The only suspected cases to arise thus far have been vCJD, although there are fears—based on animal studies—that consuming beef or beef products containing prion particles can also cause the development of classic CJD. When BSE material infects humans, the resulting disease is known as (new) variant CJD (nvCJD).
Cannibalism
has also been implicated as a transmission mechanism for abnormal prions, causing the disease known as kuru
, once found primarily among women and children of the Fore people in Papua New Guinea
. While the men of the tribe ate the body of the deceased and rarely contracted the disease, the women and children, who ate the less desirable body parts, including the brain, were 8 times more likely than men to contract kuru from infected tissue.
Prions, the infectious agent of CJD, may not be inactivated by means of routine surgical instrument sterilization
procedures. The World Health Organization
and the US Centers for Disease Control and Prevention
recommend that instrumentation used in such cases be immediately destroyed after use; short of destruction, it is recommended that heat and chemical decontamination be used in combination to process instruments that come in contact with high-infectivity tissues. No cases of iatrogenic transmission of CJD have been reported subsequent to the adoption of current sterilization procedures, or since 1976. Copper
–hydrogen peroxide
has been suggested as an alternative to the current recommendation of sodium hydroxide or sodium hypochlorite. Thermal depolymerization
also destroys prions in infected organic and inorganic matter, since the process chemically attacks protein at the molecular level.
medical journal showed that vCJD can be transmitted by blood transfusion
s. The finding alarmed healthcare officials because a large epidemic
of the disease could result in the near future. There is no test to determine if a blood donor is infected
with vCJD. In reaction to this report, the UK government banned anyone who had received a blood transfusion since January 1980 from donating blood. From 1999 there has been a ban in the UK for using UK blood to manufacture fractional products such as albumin
.
On May 28, 2002, the United States
Food and Drug Administration
instituted a policy that excludes from donation anyone who spent at least six months in certain European countries, (or three months in the United Kingdom), from 1980 to 1996. Given the large number of U.S. military personnel and their dependents residing in Europe, it was expected that over 7% of donors would be deferred due to the policy. Later changes to this policy have relaxed the restriction to a cumulative total of five years or more of civilian travel in European countries (six months or more if military). The three-month restriction on travel to the UK, however, has not been changed.
The American Red Cross
' policy is as follows:
During the period January 1, 1980, to December 31, 1996, spending a total time of three months or more in the Channel Islands
, England
, the Falkland Islands
, the Isle of Man
, Gibraltar
, Northern Ireland
, Scotland
, and Wales
precludes individuals from donating. Moreover, spending a total time of five years or more after January 1, 1980 (to present), in the above-mentioned countries and/or any country in Europe (except the former USSR), also precludes donation. People with a biologic relative who has been diagnosed with CJD or vCJD are unable to donate. Biologic relative in this setting means mother, father, sibling, grandparent, aunt, uncle or children. (For complete listing, please go to Redcross.org)
A similar policy applies to potential donors to the Australian Red Cross
' Blood Service
, precluding people who have spent a cumulative time of six months or more in the United Kingdom between 1980 and 1996.
The Singapore Red Cross
precludes potential donors who have spent a cumulative time of three months or more in the United Kingdom between 1980 and 1996.
In New Zealand, anyone who has lived in the UK, France or the Republic of Ireland for a total of six months or more between 1980 and 1996 is prohibited from donating blood.
Similar regulations are in place in Germany, where anyone who has spent six months or more living in the UK between January 1980 and December 1996 is permanently barred from donating blood.
As of 1999, Health Canada
announced a policy to defer individuals from donating blood if they have lived within the United Kingdom for one month or more from January 1, 1980, to December 31, 1996. In 2000, the same policy was applied to people who have resided in France, for at least three months from January 1980 to December 1996. Canada
will not accept blood from a person who has spent more than six months in a Western European country since January 1, 1980.
The Association of Blood Donors of Denmark precludes potential donors who have spent a cumulative time of at least 12 months in the United Kingdom between 1 January 1980 and 31 December 1996.
The Swiss Blutspendedienst SRK precludes potential donors who have spent a cumulative time of at least six months in the United Kingdom
between 1 January 1980 and 31 December 1996.
In Poland
, anyone who cumulatively spent six months or longer between 1 January 1980 and 31 December 1996 in the UK, Ireland
or France is permanently barred from donating.
In the Czech Republic
, anyone who spent more than six months in the UK or France
between the years 1980 and 1996 or received transfusion in the UK after the year 1980 is not allowed to donate blood.
, motivated by a risk of Creutzfeldt–Jakob disease, inhibiting the once popular import of, for example, Scandinavian
sperm. The risk, however, is not known, since artificial insemination
has not been studied as a route of transmission.
Diffusion Weighted Imaging (DWI) images are the most sensitive. In about 24% of cases DWI shows only cortical hyperintensity; in 68%, cortical and subcortical abnormalities; and in 5%, only subcortical anomalies.
The involvement of the thalamus can be found in sCJD, is even stronger and constant in vCJD.
Clinical testing for CJD has always been an issue. Diagnosis has mostly been based on clinical and physical examination of symptoms. In recent years, studies have shown that the tumour marker Neuron-specific enolase (NSE) is often elevated in CJD cases, however its diagnostic utility is primarily seen when combined with a test for the 14-3-3 protein
. , screening tests to identify infected asymptomatic individuals, such as blood donors, are not yet available, though methods have been proposed and evaluated.
In 2010, A team from New York described detection of PrPSc even when initially present at only one part in one hundred billion (10−11) in brain tissue. The method combines amplification with a novel technology called Surround Optical Fiber Immunoassay (SOFIA)
and some specific antibodies against PrPSc. After amplifying and then concentrating any PrPSc, the samples are labelled with a fluorescent dye using an antibody for specificity and then finally loaded into a micro-capillary tube. This tube is placed in a specially constructed apparatus so that it is totally surrounded by optical fibres to capture all light emitted once the dye is excited using a laser. The technique allowed detection of PrPSc after many fewer cycles of conversion than others have achieved, substantially reducing the possibility of artefacts, as well as speeding up the assay. The researchers also tested their method on blood samples from apparently healthy sheep that went on to develop scrapie. The animals’ brains were analysed once any symptoms became apparent. The researchers could therefore compare results from brain tissue and blood taken once the animals exhibited symptoms of the diseases, with blood obtained earlier in the animals’ lives, and from uninfected animals. The results showed very clearly that PrPSc could be detected in the blood of animals long before the symptoms appeared. After further development and testing, this method could be of
great value in surveillance as a blood or urine-based screening test for CJD.
In one third of patients with sporadic CJD, deposits of "prion protein (scrapie)," PrPSc, can be found in the skeletal muscle and/or the spleen. Diagnosis of vCJD can be supported by biopsy of the tonsils, which harbour significant amounts of PrPSc; however, biopsy
of brain tissue is the definitive diagnostic test. Due to its invasiveness, biopsy will not be done if clinical suspicion is sufficiently high or low. A negative biopsy does not rule out CJD, since it may predominate in a specific part of the brain
The classic histologic appearance is spongiform change in the gray matter: the presence of many round vacuoles from one to 50 micrometres in the neuropil
, in all six cortical layers in the cerebral cortex or with diffuse involvement of the cerebellar molecular layer. These vacuoles appear glassy or eosinophilic and may coalesce. Neuronal loss and gliosis are also seen. Plaques of amyloid-like material can be seen in the neocortex in new-variant CJD.
Unfortunately, vacuolization can be seen in other disease states. Diffuse cortical vacuolization occurs in Alzheimer's, and superficial cortical vacuolization occurs in ischemia and frontotemporal dementia. These vacuoles appear clear and punched-out. Larger vacuoles encircling neurons, vessels, and glia are a possible processing artifact.
, is infused into the patient's lateral ventricle
within the brain. PPS does not seem to stop the disease from progressing, and both brain function and tissue continue to be lost. However, the treatment is alleged to slow the progression of the otherwise untreatable disease, and may have contributed to the longer than expected survival of the seven patients who were studied. The CJD Therapy Advisory Group to the UK Health Departments advises that data are not sufficient to support claims that pentosan polysulphate is an effective treatment and suggests that further research in animal models is appropriate. A 2007 review of the treatment of 26 patients with PPS finds no proof of efficacy because of the lack of accepted objective criteria.
Scientists have investigated using RNA interference
to slow the progression of scrapie
in mice. The RNA blocks production of the protein that the CJD process transforms into prions. This research is unlikely to lead to a human therapy for many years.
Both amphotericin B
and doxorubicin
have been investigated as potentially effective against CJD, but as yet there is no strong evidence that either drug is effective in stopping the disease. Further study has been taken with other medical drugs, but none are effective. However, drugs to reduce suffering do exist, and include Valproate, an anticonvulsant, and Clonazepam, to reduce muscle jerks.
Dr. Michael Geschwind, Dr. Bruce Miller and Dr. Stanley Prusiner from University of California, San Francisco
are currently running a treatment trial for sporadic CJD using quinacrine
, a medicine originally created for malaria. Pilot studies showed quinacrine permanently cleared abnormal prion proteins from cell cultures, but results have not yet been published on the clinical study.
CDC
monitors the occurrence of CJD in the United States through periodic reviews of national mortality data. According to the CDC
:
(June 2006), a University College London team suggested that it may take more than 50 years for vCJD to develop, from their studies of kuru
, a similar disease in Papua New Guinea
. The reasoning behind the claim is that kuru was possibly transmitted through cannibalism
in Papua New Guinea
when family members would eat the body of a dead relative as a sign of mourning
. In the 1950s, cannibalism was banned. In the late 20th century, however, kuru reached epidemic proportions in certain Papua New Guinean communities, therefore suggesting that vCJD may also have a similar incubation period
of 30 to 50 years. A critique to this theory is that while mortuary cannibalism was banned in Papua New Guinea
in the 1950s, that does not necessarily mean that the practice ended. 15 years later Jared Diamond
was informed by Papuans that the practice continued. Kuru may have passed to the Fore people through the preparation of the dead body for burial.
These researchers noticed a genetic variation in some kuru patients that has been known to promote long incubation periods
. They have also proposed that individuals who contracted CJD in the early 1990s represent a distinct genetic subpopulation, with unusually short incubation periods for Bovine spongiform encephalopathy (BSE)
. This means that there may be many more vCJD patients who have longer incubation periods, which may surface many years later.
In 1997 a number of Kentuckians developed CJD. It was discovered that all the victims had consumed squirrel
brains, although a coincidental relationship between the disease and this dietary practice may have been involved.
See: http://www.guardian.co.uk/uk/2008/aug/03/bse.medicalresearch for recent concerns.
Hans Gerhard Creutzfeldt
in 1920 and shortly afterwards by Alfons Maria Jakob
, giving it the name Creutzfeldt–Jakob. Some of the clinical findings described in their first papers do not match current criteria for Creutzfeldt–Jakob disease, and it has been speculated that at least two of the patients in initial studies were suffering from a different ailment. An early description of familial CJD stems from the German psychiatrist and neurologist Friedrich Meggendorfer
(1880–1953).
Degeneration (medical)
Degeneration is deterioration in the medical sense. Generally, it is the change from a higher to a lower form. More specifically, it is the change of tissue to a lower or less functionally active form....
neurological disorder
Neurology
Neurology is a medical specialty dealing with disorders of the nervous system. Specifically, it deals with the diagnosis and treatment of all categories of disease involving the central, peripheral, and autonomic nervous systems, including their coverings, blood vessels, and all effector tissue,...
(brain
Human brain
The human brain has the same general structure as the brains of other mammals, but is over three times larger than the brain of a typical mammal with an equivalent body size. Estimates for the number of neurons in the human brain range from 80 to 120 billion...
disease
Disease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...
) that is incurable and invariably fatal. CJD is at times called a human form of mad cow disease
Bovine spongiform encephalopathy
Bovine spongiform encephalopathy , commonly known as mad-cow disease, is a fatal neurodegenerative disease in cattle that causes a spongy degeneration in the brain and spinal cord. BSE has a long incubation period, about 30 months to 8 years, usually affecting adult cattle at a peak age onset of...
, given that bovine spongiform encephalopathy
Bovine spongiform encephalopathy
Bovine spongiform encephalopathy , commonly known as mad-cow disease, is a fatal neurodegenerative disease in cattle that causes a spongy degeneration in the brain and spinal cord. BSE has a long incubation period, about 30 months to 8 years, usually affecting adult cattle at a peak age onset of...
is believed to be the cause of variant Creutzfeldt–Jakob disease in humans.
CJD is the most common among the types of transmissible spongiform encephalopathy
Transmissible spongiform encephalopathy
Transmissible spongiform encephalopathies , also known as prion diseases, are a group of progressive conditions that affect the brain and nervous system of many animals, including humans. According to the most widespread hypothesis they are transmitted by prions, though some other data suggest an...
found in humans. In CJD, the brain tissue develops holes and takes on a sponge-like texture. This is due to a type of infectious protein called a prion
Prion
A prion is an infectious agent composed of protein in a misfolded form. This is in contrast to all other known infectious agents which must contain nucleic acids . The word prion, coined in 1982 by Stanley B. Prusiner, is a portmanteau derived from the words protein and infection...
. Prions are misfolded
Protein folding
Protein folding is the process by which a protein structure assumes its functional shape or conformation. It is the physical process by which a polypeptide folds into its characteristic and functional three-dimensional structure from random coil....
proteins which replicate by converting their properly folded counterparts.
Classification
Types of CJD include:- sporadic (sCJD)
- variant (vCJD) This type is more likely to be acquired. It can be iatrogenic. It was first identified in 1996.
- familial (fCJD)
Signs and symptoms
The first symptomSymptom
A symptom is a departure from normal function or feeling which is noticed by a patient, indicating the presence of disease or abnormality...
of CJD is rapidly progressive dementia
Dementia
Dementia is a serious loss of cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging...
, leading to memory
Memory
In psychology, memory is an organism's ability to store, retain, and recall information and experiences. Traditional studies of memory began in the fields of philosophy, including techniques of artificially enhancing memory....
loss, personality
Personality psychology
Personality psychology is a branch of psychology that studies personality and individual differences. Its areas of focus include:* Constructing a coherent picture of the individual and his or her major psychological processes...
changes and hallucinations. This is accompanied by physical problems such as speech impairment, jerky movements (myoclonus
Myoclonus
Myoclonus is brief, involuntary twitching of a muscle or a group of muscles. It describes a medical sign and, generally, is not a diagnosis of a disease. Brief twitches are perfectly normal. The myoclonic twitches are usually caused by sudden muscle contractions; they also can result from brief...
), balance and coordination dysfunction (ataxia
Ataxia
Ataxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...
), changes in gait
Gait (human)
Human gait is the way locomotion is achieved using human limbs. Different gaits are characterized by differences in limb movement patterns, overall velocity, forces, kinetic and potential energy cycles, and changes in the contact with the surface .- Foot strike :One variable in different gaits is...
, rigid posture
Human position
Human positions refers to the different positions that the human body can take.There are several synonyms that refer to the human position, often used interchangeably, but having specific flavors....
, and seizures. The duration of the disease varies greatly, but sporadic (non-inherited) CJD can be fatal within months or even weeks (Johnson, 1998). In some people, the symptoms can continue for years. In most patients, these symptoms are followed by involuntary movements
Dyskinesia
Dyskinesia is a movement disorder which consists of effects including diminished voluntary movements and the presence of involuntary movements, similar to tics or choreia. Dyskinesia can be anything from a slight tremor of the hands to uncontrollable movement of, most commonly, the upper body but...
and the appearance of an atypical diagnostic electroencephalogram tracing. Most victims die 6 months after initial symptoms appear, often of pneumonia due to impaired coughing reflexes. About 15% of patients survive 2 or more years.
The symptoms of CJD are caused by the progressive death of the brain's nerve cells
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
, which is associated with the build-up of abnormal prion
Prion
A prion is an infectious agent composed of protein in a misfolded form. This is in contrast to all other known infectious agents which must contain nucleic acids . The word prion, coined in 1982 by Stanley B. Prusiner, is a portmanteau derived from the words protein and infection...
proteins forming amyloids. When brain tissue from a CJD patient is examined under a microscope
Microscope
A microscope is an instrument used to see objects that are too small for the naked eye. The science of investigating small objects using such an instrument is called microscopy...
, many tiny holes can be seen where whole areas of nerve cells have died. The word "spongiform" in "transmissible spongiform encephalopathies" refers to the sponge-like appearance of the brain tissue.
Cause
Transmissible spongiform encephalopathy diseases are caused by prionPrion
A prion is an infectious agent composed of protein in a misfolded form. This is in contrast to all other known infectious agents which must contain nucleic acids . The word prion, coined in 1982 by Stanley B. Prusiner, is a portmanteau derived from the words protein and infection...
s. The diseases are thus sometimes called prion diseases. Other prion diseases include Gerstmann–Sträussler–Scheinker syndrome (GSS), fatal familial insomnia
Fatal familial insomnia
Fatal familial insomnia is a very rare autosomal dominant inherited prion disease of the brain. It is almost always caused by a mutation to the protein PrPC, but can also develop spontaneously in patients with a non-inherited mutation variant called sporadic fatal insomnia...
(FFI) and kuru
Kuru (disease)
Kuru is an incurable degenerative neurological disorder that is a type of transmissible spongiform encephalopathy, caused by a prion found in humans...
in humans, as well as bovine spongiform encephalopathy
Bovine spongiform encephalopathy
Bovine spongiform encephalopathy , commonly known as mad-cow disease, is a fatal neurodegenerative disease in cattle that causes a spongy degeneration in the brain and spinal cord. BSE has a long incubation period, about 30 months to 8 years, usually affecting adult cattle at a peak age onset of...
(BSE, commonly known as mad cow disease) in cattle, chronic wasting disease
Chronic wasting disease
Chronic wasting disease is a transmissible spongiform encephalopathy of mule deer, whitetailed deer, elk , and moose. TSEs are caused by unusual infectious agents known as prions. To date, CWD has been found mainly in cervids...
(CWD) in elk and deer, and scrapie
Scrapie
Scrapie is a fatal, degenerative disease that affects the nervous systems of sheep and goats. It is one of several transmissible spongiform encephalopathies , which are related to bovine spongiform encephalopathy and chronic wasting disease of deer. Like other spongiform encephalopathies, scrapie...
in sheep. Alpers' syndrome in infants is also thought to be a transmissible spongiform encephalopathy caused by a prion.
The prion that is believed to cause Creutzfeldt–Jakob exhibits at least two stable conformations. One, the native state, is water-soluble and present in healthy cells. , its biological function is presumably in transmembrane transport or signaling. The other conformational state is relatively water-insoluble and readily forms protein aggregates.
People can also acquire CJD genetically through a mutation of the gene that codes for the prion protein (PRNP).
This occurs in only 5–10% of all CJD cases.
The CJD prion is dangerous because it promotes refolding
Protein folding
Protein folding is the process by which a protein structure assumes its functional shape or conformation. It is the physical process by which a polypeptide folds into its characteristic and functional three-dimensional structure from random coil....
of native proteins into the diseased state. The number of misfolded protein molecules will increase exponentially
Exponential growth
Exponential growth occurs when the growth rate of a mathematical function is proportional to the function's current value...
and the process leads to a large quantity of insoluble protein in affected cells
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
. This mass of misfolded proteins disrupts cell function and causes cell death. Mutations in the gene for the prion protein can cause a misfolding of the dominantly alpha helical regions into beta pleated sheets. This change in conformation disables the ability of the protein to undergo digestion. Once the prion is transmitted, the defective proteins invade the brain and are produced in a self-sustaining feedback loop.
Stanley B. Prusiner
Stanley B. Prusiner
Stanley Ben Prusiner is an American neurologist and biochemist. Currently the director of the Institute for Neurodegenerative Diseases at University of California, San Francisco . Prusiner discovered prions, a class of infectious self-reproducing pathogens primarily or solely composed of protein...
of the University of California, San Francisco (UCSF) was awarded the Nobel Prize in physiology or medicine
Nobel Prize in Physiology or Medicine
The Nobel Prize in Physiology or Medicine administered by the Nobel Foundation, is awarded once a year for outstanding discoveries in the field of life science and medicine. It is one of five Nobel Prizes established in 1895 by Swedish chemist Alfred Nobel, the inventor of dynamite, in his will...
in 1997 for his discovery of prions. For more than a decade, Yale University
Yale University
Yale University is a private, Ivy League university located in New Haven, Connecticut, United States. Founded in 1701 in the Colony of Connecticut, the university is the third-oldest institution of higher education in the United States...
neuropathologist Laura Manuelidis
Laura Manuelidis
Laura Manuelidis is a physician and neuropathologist at Yale University. She earned her B.A. degree from Sarah Lawrence College, where she studied poetry, and her M.D. from Yale Medical School. She is head of the section of Neuropathology in the department of Surgery at Yale. She is also on the...
has been challenging this explanation for the disease. In January 2007, she and her colleagues published an article in the Proceedings of the National Academy of Science and reported that they have found a virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
-like particle (but without finding nucleic acid
Nucleic acid
Nucleic acids are biological molecules essential for life, and include DNA and RNA . Together with proteins, nucleic acids make up the most important macromolecules; each is found in abundance in all living things, where they function in encoding, transmitting and expressing genetic information...
s so far) in less than 10% of the cells a scrapie-infected cell line and in a mouse cell line infected by a human CJD agent.
Transmission
The defective protein can be transmitted by contaminated harvested human brain products, Immunoglobulins (IVIG), corneaCornea
The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Together with the lens, the cornea refracts light, with the cornea accounting for approximately two-thirds of the eye's total optical power. In humans, the refractive power of the cornea is...
l grafts, dural grafts or electrode
Electrode
An electrode is an electrical conductor used to make contact with a nonmetallic part of a circuit...
implants (acquired or iatrogenic
Iatrogenesis
Iatrogenesis, or an iatrogenic artifact is an inadvertent adverse effect or complication resulting from medical treatment or advice, including that of psychologists, therapists, pharmacists, nurses, physicians and dentists...
form: iCJD); it can be inherited (hereditary or familial form: fCJD); or it may appear for the first time in the patient (sporadic form: sCJD). In the hereditary form, a mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
occurs in the gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
for PrP, PRNP
PRNP
Major prion protein also known as CD230 is a protein that in humans is encoded by the PRNP gene...
. Ten to 15 percent of CJD cases are inherited. (CDC)
The disease has also been shown to result from use of Human Growth Hormone obtained from the pituitary gland
Pituitary gland
In vertebrate anatomy the pituitary gland, or hypophysis, is an endocrine gland about the size of a pea and weighing 0.5 g , in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity covered by a dural fold...
s of persons who died from Creutzfeldt–Jakob Disease, though the known incidence of this cause is (as of April 2004) quite small. The risk of infection via cadaveric HGH in the US ceased when the medication was withdrawn in 1985.
It is thought that humans can contract the disease by consuming material from animals infected with the bovine form of the disease. The only suspected cases to arise thus far have been vCJD, although there are fears—based on animal studies—that consuming beef or beef products containing prion particles can also cause the development of classic CJD. When BSE material infects humans, the resulting disease is known as (new) variant CJD (nvCJD).
Cannibalism
Cannibalism
Cannibalism is the act or practice of humans eating the flesh of other human beings. It is also called anthropophagy...
has also been implicated as a transmission mechanism for abnormal prions, causing the disease known as kuru
Kuru (disease)
Kuru is an incurable degenerative neurological disorder that is a type of transmissible spongiform encephalopathy, caused by a prion found in humans...
, once found primarily among women and children of the Fore people in Papua New Guinea
Papua New Guinea
Papua New Guinea , officially the Independent State of Papua New Guinea, is a country in Oceania, occupying the eastern half of the island of New Guinea and numerous offshore islands...
. While the men of the tribe ate the body of the deceased and rarely contracted the disease, the women and children, who ate the less desirable body parts, including the brain, were 8 times more likely than men to contract kuru from infected tissue.
Prions, the infectious agent of CJD, may not be inactivated by means of routine surgical instrument sterilization
Autoclave
An autoclave is an instrument used to sterilize equipment and supplies by subjecting them to high pressure saturated steam at 121 °C for around 15–20 minutes depending on the size of the load and the contents. It was invented by Charles Chamberland in 1879, although a precursor known as the...
procedures. The World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
and the US Centers for Disease Control and Prevention
Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...
recommend that instrumentation used in such cases be immediately destroyed after use; short of destruction, it is recommended that heat and chemical decontamination be used in combination to process instruments that come in contact with high-infectivity tissues. No cases of iatrogenic transmission of CJD have been reported subsequent to the adoption of current sterilization procedures, or since 1976. Copper
Copper
Copper is a chemical element with the symbol Cu and atomic number 29. It is a ductile metal with very high thermal and electrical conductivity. Pure copper is soft and malleable; an exposed surface has a reddish-orange tarnish...
–hydrogen peroxide
Hydrogen peroxide
Hydrogen peroxide is the simplest peroxide and an oxidizer. Hydrogen peroxide is a clear liquid, slightly more viscous than water. In dilute solution, it appears colorless. With its oxidizing properties, hydrogen peroxide is often used as a bleach or cleaning agent...
has been suggested as an alternative to the current recommendation of sodium hydroxide or sodium hypochlorite. Thermal depolymerization
Thermal depolymerization
Thermal depolymerization is a depolymerization process using hydrous pyrolysis for the reduction of complex organic materials into light crude oil. It mimics the natural geological processes thought to be involved in the production of fossil fuels...
also destroys prions in infected organic and inorganic matter, since the process chemically attacks protein at the molecular level.
Blood donor restrictions
In 2004 a new report published in the LancetThe Lancet
The Lancet is a weekly peer-reviewed general medical journal. It is one of the world's best known, oldest, and most respected general medical journals...
medical journal showed that vCJD can be transmitted by blood transfusion
Blood transfusion
Blood transfusion is the process of receiving blood products into one's circulation intravenously. Transfusions are used in a variety of medical conditions to replace lost components of the blood...
s. The finding alarmed healthcare officials because a large epidemic
Epidemic
In epidemiology, an epidemic , occurs when new cases of a certain disease, in a given human population, and during a given period, substantially exceed what is expected based on recent experience...
of the disease could result in the near future. There is no test to determine if a blood donor is infected
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
with vCJD. In reaction to this report, the UK government banned anyone who had received a blood transfusion since January 1980 from donating blood. From 1999 there has been a ban in the UK for using UK blood to manufacture fractional products such as albumin
Albumin
Albumin refers generally to any protein that is water soluble, which is moderately soluble in concentrated salt solutions, and experiences heat denaturation. They are commonly found in blood plasma, and are unique to other blood proteins in that they are not glycosylated...
.
On May 28, 2002, the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
instituted a policy that excludes from donation anyone who spent at least six months in certain European countries, (or three months in the United Kingdom), from 1980 to 1996. Given the large number of U.S. military personnel and their dependents residing in Europe, it was expected that over 7% of donors would be deferred due to the policy. Later changes to this policy have relaxed the restriction to a cumulative total of five years or more of civilian travel in European countries (six months or more if military). The three-month restriction on travel to the UK, however, has not been changed.
The American Red Cross
American Red Cross
The American Red Cross , also known as the American National Red Cross, is a volunteer-led, humanitarian organization that provides emergency assistance, disaster relief and education inside the United States. It is the designated U.S...
' policy is as follows:
During the period January 1, 1980, to December 31, 1996, spending a total time of three months or more in the Channel Islands
Channel Islands
The Channel Islands are an archipelago of British Crown Dependencies in the English Channel, off the French coast of Normandy. They include two separate bailiwicks: the Bailiwick of Guernsey and the Bailiwick of Jersey...
, England
England
England is a country that is part of the United Kingdom. It shares land borders with Scotland to the north and Wales to the west; the Irish Sea is to the north west, the Celtic Sea to the south west, with the North Sea to the east and the English Channel to the south separating it from continental...
, the Falkland Islands
Falkland Islands
The Falkland Islands are an archipelago in the South Atlantic Ocean, located about from the coast of mainland South America. The archipelago consists of East Falkland, West Falkland and 776 lesser islands. The capital, Stanley, is on East Falkland...
, the Isle of Man
Isle of Man
The Isle of Man , otherwise known simply as Mann , is a self-governing British Crown Dependency, located in the Irish Sea between the islands of Great Britain and Ireland, within the British Isles. The head of state is Queen Elizabeth II, who holds the title of Lord of Mann. The Lord of Mann is...
, Gibraltar
Gibraltar
Gibraltar is a British overseas territory located on the southern end of the Iberian Peninsula at the entrance of the Mediterranean. A peninsula with an area of , it has a northern border with Andalusia, Spain. The Rock of Gibraltar is the major landmark of the region...
, Northern Ireland
Northern Ireland
Northern Ireland is one of the four countries of the United Kingdom. Situated in the north-east of the island of Ireland, it shares a border with the Republic of Ireland to the south and west...
, Scotland
Scotland
Scotland is a country that is part of the United Kingdom. Occupying the northern third of the island of Great Britain, it shares a border with England to the south and is bounded by the North Sea to the east, the Atlantic Ocean to the north and west, and the North Channel and Irish Sea to the...
, and Wales
Wales
Wales is a country that is part of the United Kingdom and the island of Great Britain, bordered by England to its east and the Atlantic Ocean and Irish Sea to its west. It has a population of three million, and a total area of 20,779 km²...
precludes individuals from donating. Moreover, spending a total time of five years or more after January 1, 1980 (to present), in the above-mentioned countries and/or any country in Europe (except the former USSR), also precludes donation. People with a biologic relative who has been diagnosed with CJD or vCJD are unable to donate. Biologic relative in this setting means mother, father, sibling, grandparent, aunt, uncle or children. (For complete listing, please go to Redcross.org)
A similar policy applies to potential donors to the Australian Red Cross
Australian Red Cross
The Australian Red Cross is one of the many national Red Cross societies around the world. The Australian organisation was established in 1914, nine days after the commencement of World War I, by Karen Tenenbaum, when she formed a branch of the British Red Cross.the organisation grew at a rapid rate...
' Blood Service
Australian Red Cross Blood Service
The Australian Red Cross Blood Service is a branch of the Australian Red Cross. It is the body primarily responsible for blood donation and related services in Australia.-History:...
, precluding people who have spent a cumulative time of six months or more in the United Kingdom between 1980 and 1996.
The Singapore Red Cross
Singapore Red Cross
The Singapore Red Cross started out in 30 September 1949 as part of the British Red Cross Society. In 6 April 1973, the Singapore Red Cross was officially incorporated by the Parliament of Singapore...
precludes potential donors who have spent a cumulative time of three months or more in the United Kingdom between 1980 and 1996.
In New Zealand, anyone who has lived in the UK, France or the Republic of Ireland for a total of six months or more between 1980 and 1996 is prohibited from donating blood.
Similar regulations are in place in Germany, where anyone who has spent six months or more living in the UK between January 1980 and December 1996 is permanently barred from donating blood.
As of 1999, Health Canada
Health Canada
Health Canada is the department of the government of Canada with responsibility for national public health.The current Minister of Health is Leona Aglukkaq, a Conservative Member of Parliament appointed to the position by Prime Minister Stephen Harper.-Branches, regions and agencies:Health Canada...
announced a policy to defer individuals from donating blood if they have lived within the United Kingdom for one month or more from January 1, 1980, to December 31, 1996. In 2000, the same policy was applied to people who have resided in France, for at least three months from January 1980 to December 1996. Canada
Canada
Canada is a North American country consisting of ten provinces and three territories. Located in the northern part of the continent, it extends from the Atlantic Ocean in the east to the Pacific Ocean in the west, and northward into the Arctic Ocean...
will not accept blood from a person who has spent more than six months in a Western European country since January 1, 1980.
The Association of Blood Donors of Denmark precludes potential donors who have spent a cumulative time of at least 12 months in the United Kingdom between 1 January 1980 and 31 December 1996.
The Swiss Blutspendedienst SRK precludes potential donors who have spent a cumulative time of at least six months in the United Kingdom
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
between 1 January 1980 and 31 December 1996.
In Poland
Poland
Poland , officially the Republic of Poland , is a country in Central Europe bordered by Germany to the west; the Czech Republic and Slovakia to the south; Ukraine, Belarus and Lithuania to the east; and the Baltic Sea and Kaliningrad Oblast, a Russian exclave, to the north...
, anyone who cumulatively spent six months or longer between 1 January 1980 and 31 December 1996 in the UK, Ireland
Ireland
Ireland is an island to the northwest of continental Europe. It is the third-largest island in Europe and the twentieth-largest island on Earth...
or France is permanently barred from donating.
In the Czech Republic
Czech Republic
The Czech Republic is a landlocked country in Central Europe. The country is bordered by Poland to the northeast, Slovakia to the east, Austria to the south, and Germany to the west and northwest....
, anyone who spent more than six months in the UK or France
France
The French Republic , The French Republic , The French Republic , (commonly known as France , is a unitary semi-presidential republic in Western Europe with several overseas territories and islands located on other continents and in the Indian, Pacific, and Atlantic oceans. Metropolitan France...
between the years 1980 and 1996 or received transfusion in the UK after the year 1980 is not allowed to donate blood.
Sperm donor restrictions
In the U.S., the FDA has banned import of any donor spermSperm donation
Sperm donation is the provision by a man, , of his sperm, with the intention that it be used to impregnate a woman who is not usually the man's sexual partner, in order to produce a child....
, motivated by a risk of Creutzfeldt–Jakob disease, inhibiting the once popular import of, for example, Scandinavian
Scandinavians
Scandinavians are a group of Germanic peoples, inhabiting Scandinavia and to a lesser extent countries associated with Scandinavia, and speaking Scandinavian languages. The group includes Danes, Norwegians and Swedes, and additionally the descendants of Scandinavian settlers such as the Icelandic...
sperm. The risk, however, is not known, since artificial insemination
Artificial insemination
Artificial insemination, or AI, is the process by which sperm is placed into the reproductive tract of a female for the purpose of impregnating the female by using means other than sexual intercourse or natural insemination...
has not been studied as a route of transmission.
Diagnosis
The diagnosis of CJD is suspected when there are typical clinical symptoms and signs such as rapidly progressing dementia with myoclonus. Further investigation can then be performed to support the diagnosis including- ElectroencephalographyElectroencephalographyElectroencephalography is the recording of electrical activity along the scalp. EEG measures voltage fluctuations resulting from ionic current flows within the neurons of the brain...
— often has characteristic triphasic spikes - Cerebrospinal fluidCerebrospinal fluidCerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...
analysis for 14-3-3 protein14-3-3 protein14-3-3 proteins are a family of conserved regulatory molecules expressed in all eukaryotic cells. 14-3-3 proteins have the ability to bind a multitude of functionally diverse signaling proteins, including kinases, phosphatases, and transmembrane receptors... - MRI of the brain — often shows high signal intensity in the caudate nucleus and putamen bilaterally on T2-weighted images.
- Research in 2010 and 2011 identified a possible blood test for CJD. The test attempts to identify the prion responsible for the disease. However, it was unable to detect the prions in those in early stages of the disease.
Diffusion Weighted Imaging (DWI) images are the most sensitive. In about 24% of cases DWI shows only cortical hyperintensity; in 68%, cortical and subcortical abnormalities; and in 5%, only subcortical anomalies.
The involvement of the thalamus can be found in sCJD, is even stronger and constant in vCJD.
Clinical testing for CJD has always been an issue. Diagnosis has mostly been based on clinical and physical examination of symptoms. In recent years, studies have shown that the tumour marker Neuron-specific enolase (NSE) is often elevated in CJD cases, however its diagnostic utility is primarily seen when combined with a test for the 14-3-3 protein
14-3-3 protein
14-3-3 proteins are a family of conserved regulatory molecules expressed in all eukaryotic cells. 14-3-3 proteins have the ability to bind a multitude of functionally diverse signaling proteins, including kinases, phosphatases, and transmembrane receptors...
. , screening tests to identify infected asymptomatic individuals, such as blood donors, are not yet available, though methods have been proposed and evaluated.
In 2010, A team from New York described detection of PrPSc even when initially present at only one part in one hundred billion (10−11) in brain tissue. The method combines amplification with a novel technology called Surround Optical Fiber Immunoassay (SOFIA)
Surround Optical Fiber Immunoassay (SOFIA)
Surround Optical Fiber Immunoassay is an ultra-sensitive, in vitro diagnostic platform incorporating a surround optical fiber assembly that captures fluorescence emissions from an entire sample. The technology's defining characteristics are its extremely high limit of detection, sensitivity and...
and some specific antibodies against PrPSc. After amplifying and then concentrating any PrPSc, the samples are labelled with a fluorescent dye using an antibody for specificity and then finally loaded into a micro-capillary tube. This tube is placed in a specially constructed apparatus so that it is totally surrounded by optical fibres to capture all light emitted once the dye is excited using a laser. The technique allowed detection of PrPSc after many fewer cycles of conversion than others have achieved, substantially reducing the possibility of artefacts, as well as speeding up the assay. The researchers also tested their method on blood samples from apparently healthy sheep that went on to develop scrapie. The animals’ brains were analysed once any symptoms became apparent. The researchers could therefore compare results from brain tissue and blood taken once the animals exhibited symptoms of the diseases, with blood obtained earlier in the animals’ lives, and from uninfected animals. The results showed very clearly that PrPSc could be detected in the blood of animals long before the symptoms appeared. After further development and testing, this method could be of
great value in surveillance as a blood or urine-based screening test for CJD.
In one third of patients with sporadic CJD, deposits of "prion protein (scrapie)," PrPSc, can be found in the skeletal muscle and/or the spleen. Diagnosis of vCJD can be supported by biopsy of the tonsils, which harbour significant amounts of PrPSc; however, biopsy
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
of brain tissue is the definitive diagnostic test. Due to its invasiveness, biopsy will not be done if clinical suspicion is sufficiently high or low. A negative biopsy does not rule out CJD, since it may predominate in a specific part of the brain
The classic histologic appearance is spongiform change in the gray matter: the presence of many round vacuoles from one to 50 micrometres in the neuropil
Neuropil
In neuroanatomy, a neuropil, which is sometimes referred to as a neuropile, is a region between neuronal cell bodies in the gray matter of the brain and blood-brain barrier . It consists of a dense tangle of axon terminals, dendrites and glial cell processes...
, in all six cortical layers in the cerebral cortex or with diffuse involvement of the cerebellar molecular layer. These vacuoles appear glassy or eosinophilic and may coalesce. Neuronal loss and gliosis are also seen. Plaques of amyloid-like material can be seen in the neocortex in new-variant CJD.
Unfortunately, vacuolization can be seen in other disease states. Diffuse cortical vacuolization occurs in Alzheimer's, and superficial cortical vacuolization occurs in ischemia and frontotemporal dementia. These vacuoles appear clear and punched-out. Larger vacuoles encircling neurons, vessels, and glia are a possible processing artifact.
- Clinical and Pathologic Characteristics:
| Characteristic | Classic CJD | Variant CJD |
|---|---|---|
| Median age at death | 68 years | 28 years |
| Median duration of illness | 4–5 months | 13–14 months |
| Clinical signs and symptoms | Dementia; early neurologic signs | Prominent psychiatric/behavioral symptoms; painful dysesthesias; delayed neurologic signs |
| Periodic sharp waves on electroencephalogram | Often present | Often absent |
| Signal hyperintensity in the caudate nucleus Caudate nucleus The caudate nucleus is a nucleus located within the basal ganglia of the brains of many animal species. The caudate nucleus is an important part of the brain's learning and memory system.-Anatomy:... and putamen Putamen The putamen is a round structure located at the base of the forebrain . The putamen and caudate nucleus together form the dorsal striatum. It is also one of the structures that comprises the basal ganglia. Through various pathways, the putamen is connected to the substantia nigra and globus pallidus... on diffusion-weighted and FLAIR MRI |
Often present | Often absent |
| Pulvinar sign-bilateral high signal intensities on axial Fluid attenuated inversion recovery (FLAIR) MRI. Also posterior thalami involvement on sagittal T2 sequences | Not reported | Present in >75% of cases |
| Immunohistochemical analysis of brain tissue | Variable accumulation. | Marked accumulation of protease-resistant prion protein |
| Presence of agent in lymphoid Lymphoid Lymphoid is a term used to describe lymph or the lymphatic system.In the context of lymphoid leukemia, it refers specifically to lymphocytes Lymphoid leukemias and lymphomas are now considered to be tumors of the same type of cell lineage. They are called "leukemia" when in the blood or marrow and... tissue |
Not readily detected | Readily detected |
| Increased glycoform ratio on immunoblot analysis of protease-resistant prion protein |
Not reported | Marked accumulation of protease-resistant prion protein |
| Presence of amyloid plaques in brain tissue | May be present | May be present |
- An abnormal signal in the posterior thalamus on T2- and diffusion-weighted images and fluid-attenuated inversion recovery sequences on brain magnetic resonance imaging (MRI); in the appropriate clinical context, this signal is highly specific for vCJD. (Source: CDC)
Treatment
no generally accepted treatment for CJD exists; the disease is invariably fatal and research continues. An experimental treatment was given to a Northern Irish teenager, Jonathan Simms, beginning in January 2003. The medication, called pentosan polysulphate (PPS) and used to treat interstitial cystitisInterstitial cystitis
Interstitial cystitis or bladder pain syndrome is a chronic, oftentimes severely debilitating disease of the urinary bladder...
, is infused into the patient's lateral ventricle
Ventricular system
The ventricular system is a set of structures containing cerebrospinal fluid in the brain. It is continuous with the central canal of the spinal cord.-Components:The system comprises four ventricles:* right and left lateral ventricles* third ventricle...
within the brain. PPS does not seem to stop the disease from progressing, and both brain function and tissue continue to be lost. However, the treatment is alleged to slow the progression of the otherwise untreatable disease, and may have contributed to the longer than expected survival of the seven patients who were studied. The CJD Therapy Advisory Group to the UK Health Departments advises that data are not sufficient to support claims that pentosan polysulphate is an effective treatment and suggests that further research in animal models is appropriate. A 2007 review of the treatment of 26 patients with PPS finds no proof of efficacy because of the lack of accepted objective criteria.
Scientists have investigated using RNA interference
RNA interference
RNA interference is a process within living cells that moderates the activity of their genes. Historically, it was known by other names, including co-suppression, post transcriptional gene silencing , and quelling. Only after these apparently unrelated processes were fully understood did it become...
to slow the progression of scrapie
Scrapie
Scrapie is a fatal, degenerative disease that affects the nervous systems of sheep and goats. It is one of several transmissible spongiform encephalopathies , which are related to bovine spongiform encephalopathy and chronic wasting disease of deer. Like other spongiform encephalopathies, scrapie...
in mice. The RNA blocks production of the protein that the CJD process transforms into prions. This research is unlikely to lead to a human therapy for many years.
Both amphotericin B
Amphotericin B
Amphotericin B is a polyene antifungal drug, often used intravenously for systemic fungal infections...
and doxorubicin
Doxorubicin
Doxorubicin INN is a drug used in cancer chemotherapy. It is an anthracycline antibiotic, closely related to the natural product daunomycin, and like all anthracyclines, it works by intercalating DNA....
have been investigated as potentially effective against CJD, but as yet there is no strong evidence that either drug is effective in stopping the disease. Further study has been taken with other medical drugs, but none are effective. However, drugs to reduce suffering do exist, and include Valproate, an anticonvulsant, and Clonazepam, to reduce muscle jerks.
Dr. Michael Geschwind, Dr. Bruce Miller and Dr. Stanley Prusiner from University of California, San Francisco
University of California, San Francisco
The University of California, San Francisco is one of the world's leading centers of health sciences research, patient care, and education. UCSF's medical, pharmacy, dentistry, nursing, and graduate schools are among the top health science professional schools in the world...
are currently running a treatment trial for sporadic CJD using quinacrine
Quinacrine
Quinacrine is a drug with a number of different medical applications. It is related to mefloquine.-Uses:Its main effects are as an antiprotozoal, antirheumatic and an intrapleural sclerosing agent....
, a medicine originally created for malaria. Pilot studies showed quinacrine permanently cleared abnormal prion proteins from cell cultures, but results have not yet been published on the clinical study.
Epidemiology
Although CJD is the most common human prion disease, it is still rare, occurring in about one out of every one million people every year. It usually affects people aged 45–75, most commonly appearing in people between the ages of 60–65. The exception to this is the more recently-recognised 'variant' CJD (vCJD), which occurs in younger people.CDC
Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...
monitors the occurrence of CJD in the United States through periodic reviews of national mortality data. According to the CDC
Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...
:
- CJD occurs worldwide at a rate of about 1 case per million population per year.
- On the basis of mortality surveillance from 1979 to 1994, the annual incidenceIncidence (epidemiology)Incidence is a measure of the risk of developing some new condition within a specified period of time. Although sometimes loosely expressed simply as the number of new cases during some time period, it is better expressed as a proportion or a rate with a denominator.Incidence proportion is the...
of CJD remained stable at approximately 1 case per millionMillionOne million or one thousand thousand, is the natural number following 999,999 and preceding 1,000,001. The word is derived from the early Italian millione , from mille, "thousand", plus the augmentative suffix -one.In scientific notation, it is written as or just 106...
persons in the United States. - In the United States, CJD deaths among persons younger than 30 years of age are extremely rare (fewer than five deaths per billion1000000000 (number)1,000,000,000 is the natural number following 999,999,999 and preceding 1,000,000,001.In scientific notation, it is written as 109....
per year). - The disease is found most frequently in patients 55–65 years of age, but cases can occur in people older than 90 years and younger than 55 years of age.
- In more than 85% of cases, the duration of CJD is less than 1 year (median: four months) after onset of symptoms.
New concerns
In The LancetThe Lancet
The Lancet is a weekly peer-reviewed general medical journal. It is one of the world's best known, oldest, and most respected general medical journals...
(June 2006), a University College London team suggested that it may take more than 50 years for vCJD to develop, from their studies of kuru
Kuru (disease)
Kuru is an incurable degenerative neurological disorder that is a type of transmissible spongiform encephalopathy, caused by a prion found in humans...
, a similar disease in Papua New Guinea
Papua New Guinea
Papua New Guinea , officially the Independent State of Papua New Guinea, is a country in Oceania, occupying the eastern half of the island of New Guinea and numerous offshore islands...
. The reasoning behind the claim is that kuru was possibly transmitted through cannibalism
Cannibalism
Cannibalism is the act or practice of humans eating the flesh of other human beings. It is also called anthropophagy...
in Papua New Guinea
Papua New Guinea
Papua New Guinea , officially the Independent State of Papua New Guinea, is a country in Oceania, occupying the eastern half of the island of New Guinea and numerous offshore islands...
when family members would eat the body of a dead relative as a sign of mourning
Mourning
Mourning is, in the simplest sense, synonymous with grief over the death of someone. The word is also used to describe a cultural complex of behaviours in which the bereaved participate or are expected to participate...
. In the 1950s, cannibalism was banned. In the late 20th century, however, kuru reached epidemic proportions in certain Papua New Guinean communities, therefore suggesting that vCJD may also have a similar incubation period
Incubation period
Incubation period is the time elapsed between exposure to a pathogenic organism, a chemical or radiation, and when symptoms and signs are first apparent...
of 30 to 50 years. A critique to this theory is that while mortuary cannibalism was banned in Papua New Guinea
Papua New Guinea
Papua New Guinea , officially the Independent State of Papua New Guinea, is a country in Oceania, occupying the eastern half of the island of New Guinea and numerous offshore islands...
in the 1950s, that does not necessarily mean that the practice ended. 15 years later Jared Diamond
Jared Diamond
Jared Mason Diamond is an American scientist and author whose work draws from a variety of fields. He is currently Professor of Geography and Physiology at UCLA...
was informed by Papuans that the practice continued. Kuru may have passed to the Fore people through the preparation of the dead body for burial.
These researchers noticed a genetic variation in some kuru patients that has been known to promote long incubation periods
Incubation period
Incubation period is the time elapsed between exposure to a pathogenic organism, a chemical or radiation, and when symptoms and signs are first apparent...
. They have also proposed that individuals who contracted CJD in the early 1990s represent a distinct genetic subpopulation, with unusually short incubation periods for Bovine spongiform encephalopathy (BSE)
Bovine spongiform encephalopathy
Bovine spongiform encephalopathy , commonly known as mad-cow disease, is a fatal neurodegenerative disease in cattle that causes a spongy degeneration in the brain and spinal cord. BSE has a long incubation period, about 30 months to 8 years, usually affecting adult cattle at a peak age onset of...
. This means that there may be many more vCJD patients who have longer incubation periods, which may surface many years later.
In 1997 a number of Kentuckians developed CJD. It was discovered that all the victims had consumed squirrel
Squirrel
Squirrels belong to a large family of small or medium-sized rodents called the Sciuridae. The family includes tree squirrels, ground squirrels, chipmunks, marmots , flying squirrels, and prairie dogs. Squirrels are indigenous to the Americas, Eurasia, and Africa and have been introduced to Australia...
brains, although a coincidental relationship between the disease and this dietary practice may have been involved.
See: http://www.guardian.co.uk/uk/2008/aug/03/bse.medicalresearch for recent concerns.
History
The disease was first described by German neurologistNeurologist
A neurologist is a physician who specializes in neurology, and is trained to investigate, or diagnose and treat neurological disorders.Neurology is the medical specialty related to the human nervous system. The nervous system encompasses the brain, spinal cord, and peripheral nerves. A specialist...
Hans Gerhard Creutzfeldt
Hans Gerhard Creutzfeldt
Hans Gerhard Creutzfeldt was a German neuropathologist, who first described the Creutzfeldt-Jakob disease. He was born in Harburg upon Elbe and died in Munich.-Biography:...
in 1920 and shortly afterwards by Alfons Maria Jakob
Alfons Maria Jakob
Alfons Maria Jakob was a German neurologist with important contributions on neuropathology....
, giving it the name Creutzfeldt–Jakob. Some of the clinical findings described in their first papers do not match current criteria for Creutzfeldt–Jakob disease, and it has been speculated that at least two of the patients in initial studies were suffering from a different ailment. An early description of familial CJD stems from the German psychiatrist and neurologist Friedrich Meggendorfer
Friedrich Meggendorfer
Friedrich Meggendorfer was a German psychiatrist and neurologist.- Life :Born in Bad Aibling, Bavaria, he was intended to take over the local colonial goods store of his ancestors. He enjoyed an excellent international education aimed at preparing him for this role...
(1880–1953).
External links
- UCSF Memory and Aging Center - education website from a CJD patient care and research center
- UCSF Memory and Aging Center YouTube channel with films about CJD
- Institute for Neurodegenerative Diseases (IND) - a basic science research institute working on a cure for CJD