PRION DISEASE

What is prion disease ?

The word prion is derived from the word infection and protein .

Prion diseases or transmissible spongiform encephalopathies (TSEs) are a family of rare progressive neurodegenerative disorders ( loss of structure or function of neurons, including death of neurons. ) that affect both humans and animals. known as "mad cow disease" in cattle and “Creutzfeldt -Jakob disease” (CJD) in humans.

in the year 1986 farmers recognized that something was happening to their cattle.

In farming, it is convenient and healthy for cattle to be fed soybean meal as a part of their diet.

In England, soybeans don’t grow well, so British farmers fed their cattle an animal byproduct which contained the mixed meat and bones of cattle and sheep.

This practice caused the infected brains, nervous systems, and blood of infected cattle to be fed to other cows, thus filling them with an accumulation of infected meat. Obviously, more and more cows became infected and more and more cattle began to die.

THE HISTORY OF PRION

also the massive use of hormones, pesticides and other harmful substances which destroy the animal's immune system. When these diseased animals are eaten by people, then the people get sick and die.

Prions propagate by transmitting a misfolded protein state. When a prion enters a healthy organism, it induces

existing, properly folded proteins -which is found most abundantly in the brain- to convert into the disease-associated, prion form.

Alteration in the conformation of the protein where normal α-helix structure is converted to β-sheet structure.

the prion acts as a template to guide the misfolding of more protein into prion form.

These newly formed prions can then go on to convert more proteins themselves; this triggers a chain reaction that produces large amounts of the prion form.

Aggregations of these abnormal isoforms form highly structured amyloid fibers, which accumulate to form plaques.

CAUSES OF PRION

All known mammalian prion diseases are caused by the so-called prion protein, PrP.

The endogenous, properly folded, form is denoted PrPC (for Common or Cellular) while the disease-linked, misfolded form is denoted PrPSc (for Scrapie )

Three-dimensional structure of PrP C (left) and proposed 3D structure of PrP Sc (right). Alpha helices are indicated in green while beta sheets are indicated in blue. PrP C is composed primarily of alpha helices while PrP Sc is composed primarily of Beta pleated sheets.

Left: normal prion protein (coloured green) in non-infected mouse cell cultures. Right: misfolded prion form (coloured green) in infected cell which accumulate primarily in vesicles within the cell. Cell nuclei are edepicted in blue.

This altered structure is extremely stable, insoluble and accumulates in infected tissue, causing tissue damage and cell death

This structural stability means that prions are resistant to denaturation by chemical and physical agents, making disposal and containment of these particles difficult.

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It has an incubation period of months to years during which there are no symptoms, even though the pathway of converting the normal brain PrP protein into the toxic, disease-related PrPSc form has started. At present, there is virtually no way to detect PrPSc reliably except by examining postmortem brain tissue where the brain is spongy in form due to death of neurons .

Symptoms in Cattle

Difficulty in standing ,difficulty to walk , loss of coordination and weight loss despite well feeding accompanied by reduction in milk production.

One may even observe slight change in behavior and attitude of the animal that is affected by mad cow disease.

Behavioural Symptoms Often mood disturbance e.g. aggression or

loss of interest and personality changes persist into the illness. 

Anxiety and depression are fairly common features.  There may also be a lack of social judgment and disinhibition. 

People may prefer to keep to familiar routines, changes in the regular daily pattern of events, or new faces may cause distress and anxiety.

Communication Problems Speech tends to become slurred (dysarthria) and

quiet and as a result speech may become hard to understand, making communication difficult. 

There is often a reduction in the content of language, word finding difficulties and there may be repetition of words or sentences.  Eventually the person can become mute. 

As the illness progresses the ability to read and write are gradually lost.  Problems may occur with understanding written material and with spelling and signing forms; the person may also have difficulty following instructions.

Memory/Cognitive Deficits Problems develop with memory and thinking

and there is often a general decline in intellect. 

There may be forgetfulness of day to day events, often accompanied by disorientation and poor concentration or attention. 

Everyday skills that we take for granted may be lost.  Typically the person affected will forget the day and date.  They may also start to forget how to carry out everyday skills, for example making a cup of tea.  In the latter stages of the disease the person may become increasingly unaware of their immediate environment and the people around them.

Movement Problems Initially there may be a disturbance in balance and

gait, leading to unsteadiness (ataxia).  Walking will therefore be affected and so extra care will have to be taken to try to prevent falls.

  Involuntary rhythmic muscle contractions leading to jerky movements (myoclonus) and difficulties coordinating hand movements leading to apparent clumsiness.  Shakiness (tremor) and stiffness (rigidity) are often seen.

  As movements become increasingly uncoordinated the individual will need help with carrying out their daily activities, for example, personal hygiene and use of the toilet.

Swallowing Problems With the progression of the disease there may also be

difficulty in swallowing.  There are a number of strategies, which may make swallowing easier and an assessment by a speech and language therapist can identify problems and give advice regarding strategies to help.

As swallowing becomes increasingly difficult in the later stages of the disease, it may be suggested that nutrition be supplemented with tube feeding.  This issue will require careful consideration and is rarely done in prion disease.  Relatives need support in making an informed decision.  A speech and language therapist, Macmillan nurse, dietician as well as your own GP may be able to offer advice.

Visual/Perceptual Problems Visual problems include double vision and difficulty

moving eyes to follow objects. Hallucinations are fairly common.  There may be a failure to understand and correctly interpret visual stimuli.  There may be misidentification of objects/people, whereby something/someone may not be recognized accurately.

Some patients may suffer from what is known as cortical blindness, a condition in which an individual appears to be blind (although the eyes themselves are normal), due to damage in the visual processing and interpretation areas of the brain.

Seizures

Very occasionally a person may suffer from seizures in the later stages of the disease.

Medication is available to help control seizures should they occur.

Other symptoms Personality changes Psychiatric problems Depression Lack of coordination Unsteady gait Myoclonus Unusual sensations Insomnia Confusion Memory problems Severe mental impairment Inability to move Inability to speak 

It has been hard to develop a test for prion disease because the body’s immune system does not fight off prion infection by making antibodies in the same way it does against germs like bacteria or viruses.

It has been challenging to develop a test that can distinguish between the normal prion protein, which we all have in our blood, and the abnormal form linked to the disease which is chemically very similar

TEST

At present, the best diagnostic tests for CJD use cerebral spinal fluid or actual brain tissue as test samples; neither is easily obtained Moreover, the current spinal fluid-based tests are not fully sensitive or specific for CJD

.Scientists have developed a prototype test. This involves taking a small blood sample from a patient as with any other blood test.

A small sample of blood is mixed with special metal beads to which the rogue prion proteins stick tightly.

These are then washed to remove the normal prion protein and other blood components that would interfere with the test.

Finally, the amount of rogue prion protein attached to the beads is measured using antibodies we have developed that bind very tightly to the prion protein.

At present the test does not work in other forms of prion disease such as sporadic CJD but we are hoping this will be possible with further work in the future. 

Prions disease is a fungal infection and is caused by a protein.

There are ways to control, prevent and infections from spreading.

No treatment has been confirmed to be a definite cure for prions disease.

Let`s remember that; Prions cause neurodegenerative disease by aggregating extracellularly within the central nervous system to form plaques known as amyloid

TREATMENT

Dr. Wisniewski and his colleagues found 68 chemical compounds, known as styryl-based compounds, his team screened these 68 styryl-based compounds for their ability to inhibit prion infection in a standard cell culture.

They found two that seemed both effective and non-toxic, and confirmed their effectiveness by showing that on average they markedly delayed the onset of symptoms in prion-injected lab mice.

The styryl-based compounds also reduced the signs of disease in the mouse

.they found similar results the antidepressant trimipramine and the anti-scizophrenia drug fluphenazine Both are chemically related to the anti-protozoal drug quinacrine, which is known to slow prion infection in cell cultures,

Although it fails to protect prion-infected mice or humans. Their chemical differences from quinacrine apparently enable the two drugs to bind more tightly to toxic prion aggregates, and-like the styryl-based compounds-prevent these aggregates from assembling new copies of themselves.

"One of the trimipramine-treated mice stayed healthy throughout the 400-day"….. Dr. Wisniewski's laboratory's work to develop potential prion-disease vaccines.

References http://www.drday.com/madcow.htm http://

library.thinkquest.org/05aug/00112/mad_cow_frameset.htm

http://www.cdc.gov/ncidod/dvrd/prions/ http://en.wikipedia.org/wiki/Prion http://

www.helmholtz.de/index.php?id=2224&L=1&type=0

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