Student guest post: Captain, our sensors have detected Prions moving into the Medula Oblangata!

Student guest post by Bradley Christensen

No, this isn’t a clip from a science fiction movie.  Although dramatic, this does occur in the brains of some people and animals around on our home planet.  What is a prion you ask?  Prions are almost as mysterious to the scientists that research them as they are to me, you and the neighbor down the street.  Prion is a term used to describe an abnormal and particularly destructive strand of protein found in the brain.  Proteins are the building blocks of the muscles and tissues of our bodies that work combine together to perform different functions.  Prions are in their most basic form just an abnormal protein.  They create damage by causing neighboring proteins (in the brain tissue) to become abnormal and misshapen as well.  Like a house of cards, the structure of the brain tissue begins to break down.  When pathologists look at tissue samples from brains affected by prions, they find multiple holes like cutting through a section of sponge.  Thus giving this condition the medical term “spongiform encephalopathy.“
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Microscopic picture of affected brain tissue from Wikipedia commons

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 Computerized model of prion from Wikipedia commons

Diseases caused by prions are generally termed TSE (transmissible spongiform encephalopathy).  Some of these diseases occur spontaneously and some are transferred from one infected animal (or human) to another.  We know that the prion can occur be passed from mother to offspring, through bodily fluids, or by ingestion [8] of or exposure to brain or spinal tissue of an infected animal [6] or man (Zombie fanatics, may I please have your attention back.)

Prions are unique because like cancer cells, the body can’t recognize them as abnormal and mount an immune response against them.  Also, we have not developed an effective way of testing for prions until after the patient has already died. A third concern is that prions cannot be destroyed or controlled by chemicals, medications and treatments that we have available for other diseases. They are very hardy and seem to be unaffected by traditional and even extreme means of disinfection like ionizing or ultraviolet radiation and even formalin.

The Prion Family

TSE’s have been found in humans, cervids (elk, deer, moose), mink, sheep and goats, and even cats.  Listed below are several.

Scrapie (sheep and goats)

Brad pic 3Scrapie was first discovered in the United States in 1947[2] and causes progressive neurologic and behavioral changes in sheep and goats that eventually lead to death.  There is no treatment and the only way to diagnose is post mortem examinations of brain tissue however, a test has been developed to identify susceptible live animals.  Scrapie is thought to be transferred from mother to offspring during pregnancy.

The USDA began actively monitoring this disease in 2003 and started the RSSS (Regulatory Scrapie Slaughter Surveillance) program.[3] This is a voluntary program that allows flock owners to test and identify susceptible animals and are compensated for having these animals removed from the flocks.   Animals are also tested at the time of slaughter and any infected animals are traced back to the producers and allow them to further identify infected or exposed animals in their flocks for voluntary removal.   Research is ongoing to find better ways to detect infected live animals.   In laboratory environments, scientists have been able to transmit scrapie to other species but there is no evidence linking its potential spread to humans [2].

Chronic Wasting Disease (CWD)

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CWD was first seen in the U.S. in 1967 but it wasn’t until 1978 that a prion was discovered to be the cause [3].  Similar to other TSE’s, this disease cause a progressively fatal neurologic disease in deer, elk and moose.  Much less is known about this disease but it is thought to be spread by direct contact with saliva feces or urine from infected animals.  Through surveillance programs started in 2002 [3], this disease has been found in both wild and domestic deer, elk and moose in multiple states.  Research and control is much more difficult since the vast majority of these species are wild.  There is no evidence of this condition being spread to humans.

Bovine Spongioform Encephalopathy (BSE)  “Mad Cow Disease”

BSE or Mad Cow Disease has been a hot topic over the past 15 years since its possible link to humans.  Just like scrapie and CWD in their prospective animals, BSE causes a fatal TSE in cows.  The name “Mad Cow dbrad pic 5isease” came from the symptoms that are observed in some cows with this disease.   This prion disease is transmitted through ingestion of brain or nervous system tissues of infected animals.  It used to be common practice to feed ground bone meal from deceased animals to live animals as a source of mineral but since the discovery of this disease transmission, the practice has been almost universally discontinued.  Unlike TSE’s in other species, the medical and research community has discovered a link between cows and man.[5]

Human prion diseases – CJD (Creutzfeldt-Jakob Disease), Kuru, vCJD.

There are several types and descriptions of prion diseases in people.  These TSE’s are much more studied and researched because they affect humans.  All of these conditions are a TSE but have variations based on how they are transmitted and differences in symptoms.  CJD has been seen since the 1920’s [7] and Kuru was discovered in cannibalistic tribes in New Guinea in 1957 [8].   The occurrence of prion diseases in humans varies from sporadic (unknown cause), iatrogenic (inadvertent transplant of infected tissue like corneal grafts), to genetic predisposition (familial CJD) and even ingestion of infected tissues (Kuru – human cannibalism and variant CJD – infected cattle).  The onset and length of symptomatic disease and death in humans varies between these types of prion diseases but are always fatal.

Overall, prion disease in humans is rare with 1-2 deaths per 1 million people in the population worldwide but it does tend to be more common after the age of 50 with 3.4 deaths per 1 millions [7].

brad pic 6Am I going to get this disease? 

Probably not.  Statistically, TSE is rare in humans.  You are much more likely to develop any number of common types of cancer or even be struck by lightning than to develop prion disease.

Then why are prions a concern?

They are scary because they look normal to your body, we can’t test for them while the person or animal is still alive and they are not susceptible to any types of treatments that we have available.  TSE is rare in people but always fatal.

Is there anything I can do to protect myself? 

If you’re a cannibal, please seek intervention right away.  Wild game hunters, the CDC recommends that you consult state health departments regarding precautions in states that have cases of CWD.  You should generally avoid hunting sick or abnormal appearing animals, reduce exposure to brain or spinal tissues and where gloves.  Overall there is little you can do to personally limit your risk.

Is anyone trying to protect us? 

Definitely.  Massive amounts of research has been underway all over the world to try and understand prions and find ways to test and combat them.  The WHO (World Health Organization) has created guidelines regarding food supply, human tissue handing and use for research and medical purposes as well as handling of.  The United States also has very rigorous regulations and monitoring in cattle populations in our country.  At this time, we are considered BSE free country and our food supply safe.  Other countries are following suit to protect the food supply on a global basis.

Where do I learn more?

There are many good resources but there are many bad ones too.  Good places to consult is the CDC (Centers for Disease Control), APHIS (Animal and Plant Health Inspection Service) or your local and state public health services.

Should I avoid contact with types of animals that can have prion disease? 

No, except in the normal precautions around wildlife.  We have no evidence that prions are transmitted from animals to humans other than with BSE as mentioned above.  You are at more risk of being trampled by an animal than catching prions from it.

 References:

  1. USDA/APHIS/VS (2004).  Scrapie Fact Sheet.  Retrieved from http://www.aphis.usda.gov/animal_health/animal_diseases/scrapie/downloads/fs_ahscrapie.pdf  – scrapie Fact sheet
  2. RSSS program http://www.aphis.usda.gov/publications/animal_health/content/printable_version/fs_scrafcp.pdf
  3. USDA/APHIS (2013). Chronic Wasting Disease.  Retrieved from http://www.aphis.usda.gov/animal_health/animal_diseases/cwd/history.shtml
  4. USDA/APHIS (2012).  About BSE. Retrieved from http://www.aphis.usda.gov/newsroom/hot_issues/bse/index.shtml  BSE aphis
  5. Will RG, Ironside JW, Zeidler M, Cousens SN, Estibeiro K, Alperovitch A, Poser S, Pocchiari M, Hofman A , Smith PG (1996) Apr. 6. A new variant of Creutzfeldt-Jakob Disease in UK.  Lancet 347(9006):921-5
  6. 6.      Johnson, Richard T. (2005).  Prion Diseases. The Lancet Neurology, Vol. 4, Iss. 10, 635-42

http://www.sciencedirect.com.proxy.lib.uiowa.edu/science/article/pii/S1474442205701927

7.  Centers for Disease Control and Prevention (CDC) (2012). Creutzfeldt-Jakob Disease.

Retrieved from  http://www.cdc.gov/ncidod/dvrd/cjd/

8.   Gajdusek, V. Z. (1957). Degenerative disease of the nervous system in New Guinea: the

Endemic occurrence of “kuru” in the native population.  N Engl J Med, 257, 974-978

9.   World Health Organization (WHO) (2012). Variant Creutzfeldt-Jakob Disease.

Retrieved from http://www.who.int/mediacentre/factsheets/fs180/en/

  1. http://commons.wikimedia.org/wiki/File:BOVINE_PRION_PROTEIN_1dx0_asym_r_500. – prion

picture

  1. http://commons.wikimedia.org/wiki/File:Histology_bse.jpg – histology picture

12. http://www.aphis.usda.gov/animal_health/videos/scrapie-narrated.mpg   (scrapie

Video hyperlink)

13.  BSE information – bseinfo.org   retrieved from

http://www.bseinfo.org/deactivationofprions.aspx

All photographs in this blog are for public domain found on http://creativecommons.org/

Reviewing the big P…Prions!

Student guest post by Rajeshwari Nair

Discussion on consumption of meat products is a common occurrence in my household. Hailing from India, I have always relished meat dishes that my mom cooks up, hot and spicy! However, there is always a nagging guilt on eating animals. People have tried convincing me that we are all part of the food-chain in this ecosystem, so either eat or be eaten. However, in recent times one thought crosses my mind when I stuff that yummy piece of meat in my salivating mouth, will this karma get to me soon? Will my brain dissolve as I chew on the brain of this mute four-legged creature? All this began not very long after my first lecture on ‘Prion diseases’. I sit in class thinking, ‘Hey we are built of protein matter, we eat forms of protein daily, we digest proteins daily and look at what a tiny solitary protein can do to us.’

Prions (pronounced pree-ons) are an acronym for proteinacious infectious particles. A normal prion protein, designated as PrPc is produced by every cell in a human body. This protein is encrypted by a highly conserved gene PrP in the human genome (chromosome 20) [5]. Okay all this sounds just fine, so what about this protein? Well believe it or not, it has a life of its own. Yes, superior to viruses and bacteria and it does not need a DNA or RNA to survive or infect other living forms.
Prion protein has a beautiful structure made of alpha helix sheets. This protein can be digested by enzymes generally used to breakdown proteins. However, something goes awry and this awe-inspiring protein changes to a structure with several beta sheets. What transpires here is really not well understood. However, there have been several hypotheses, what we know better as educated guess! The protein gets misfolded (PrPsc) and leads to further misfolding of normal PrPc. Thus there is a school of thought that the ‘first misfolded prion protein’ may be the infectious agent [1]. However, propagation process does not stop at this. These misfolded proteins form plaques and thus begins the destruction of a thinking organ, the brain. Hey, but why did the first prion protein misfold. It could be due to something you inherited from your parents, something you ate at your favorite food joint, a mutation or just like that…research is ongoing!

Abnormal prion proteins cause a spectrum of diseases known as transmissible spongiform encephalopathy or TSE. Prion diseases are progressive, neurodegenerative disorders that affect animals as well as humans. The disease spectrum includes gory sounding conditions in humans such as true Cruetzfeld-Jakob Disease (CJD), Kuru (spread by ritualistic cannibalism), Fatal Familial Insomnia, and Gerstmann-Sträussler-Scheinker syndrome [4]. Remember the ‘Mad Cow disease’ which caused chaos in England way back in 1986. Farmers back then fed their cattle soybean. However soybean did not grow well, so these farmers found an alternative. They fed their cattle animal byproducts, brain, blood, bones from other cattle and sheep. Hmm…I am thinking ‘animal cannibalism’. Anyways, these infected cows found their way to markets in England, either as fuel (food) or fertilizer (manure). People who came in contact with these infected animals soon took ill, and contracted what is known as Variant form of CJD (vCJD). At least 157 people were infected and killed till 2004. United States has not been oblivious to this disease. Holman et al., reported an analysis of death certificates of US residents which estimated 6,917 deaths with CJD, 1979-2006. Most of these deaths were among people 65 years and older and mostly whites. At least three patients have died of vCJD since 2004 [2]. Occurrence of prion diseases could be familial (inheritance of mutated prion genes), just out of the blue with no known cause (sporadic), ingestion of infected material, and even through transplant of infected organs such as the brain, ocular tissue or human pituitary growth hormone [4]. Signs and symptoms depend on part of the brain infected and age at infection. Disease symptoms can be easily mistaken for other neurological conditions such as Alzheimer’s, Parkinson’s or even just depression. Prions can turn our brain into a complete mush which may not be diagnosed until an autopsy is performed. Something to ponder about may be…increase in mental health conditions such as Alzheimer’s, dementia and others. Ever speculate there may be a prion disease since above mentioned conditions are often clinically diagnosed.

It is time to further investigate this situation and fill in existing gaps in knowledge. Various forms of therapy are under investigation with focus on preventing structural changes to the normal prion, thus preventing disease. Drugs which can cross the blood brain barrier are being considered to combat prions. Some antimalarial drugs such as Mepacrine, an anti-tumoral drug Iododoxorubicin and even Tetracycline are being considered potential for anti-prion therapy. Some of these drugs have been tested on animal models and cell cultures, and have shown robust effects. Even a vaccine was being tested by clinical trial as a method to slow disease progression [3].

Even though all these facts sound alarming, one may be lead to think why should we care. There are hardly any cases occurring, there are several other battle to be fought. This one can be laid to rest for now. On the contrary, in today’s world with new emerging and re-emerging diseases prions could be a significant assault on living forms. Also, globalization and environmental interactions could act as fuel to this fire. We hear of diseases being transmitted from animals to human (zoonotic) and the reverse. Is there a chance that prion diseases could add to this list?

References:

1. Gains MJ, LeBlanc AC. (2007). Canadian Association of Neurosciences Review: Prion protein and prion diseases: The good and the bad. The Canadian Journal of Neurological Sciences, 34: 126-145.

2. Holman RC, Belay ED, Christensen KY, Maddox RA, Minino AM, Folkema AM, et al. Human prion diseases in the United States. PLoS ONE. 5;1:e8521.

3. Caramelli M, Ru G, Acutis P, Forloni G. Prion Diseases Current understanding of epidemiology and pathogenesis and therapeutic advances. CNS Drugs. 20;1:15-28.
4. Pedersen NS, Smith E. Prion diseases: Epidemiology in man. Acta Pathologica, Microbiologica et Immunologica Scandinavica. 110:14-22.

5. Glatzel M, Stoeck K, Seeger H, Lührs T, Aguzzi A. Human prion diseases:molecular and clinical aspects. Archives of Neurology. 2005;62:545-52.