Tag Archives: prions

Origins of CWD in Europe

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Chronic wasting disease (CWD) is a relentless epidemic disorder caused by infectious prions that threatens the survival of cervid populations and raises increasing public health concerns in North America. In Europe, CWD was detected for the first time in wild Norwegian reindeer (Rangifer tarandus) and moose (Alces alces) in 2016. In this study, we aimed at comparing the strain properties of CWD prions derived from different cervid species in Norway and North America.

Using a classical strain typing approach involving transmission and adaptation to bank voles (Myodes glareolus), we found that prions causing CWD in Norway induced incubation times, neuropathology, regional deposition of misfolded prion protein aggregates in the brain, and size of their protease-resistant core, different from those that characterize North American CWD. These findings show that CWD prion strains affecting Norwegian cervids are distinct from those found in North America, implying that the highly contagious North American CWD prions are not the proximate cause of the newly discovered Norwegian CWD cases.

In addition, Norwegian CWD isolates showed an unexpected strain variability, with reindeer and moose being caused by different CWD strains. Our findings shed light on the origin of emergent European CWD, have significant implications for understanding the nature and the ecology of CWD in Europe, and highlight the need to assess the zoonotic potential of the new CWD strains detected in Europe.

Studies in bank voles reveal strain differences between chronic wasting disease prions from Norway and North America

PNAS

Romolo Nonno, Michele A. Di Bari, Laura Pirisinu, Claudia D’Agostino, Ilaria Vanni, Barbara Chiappini, Stefano Marcon, Geraldina Riccardi, Linh Tran, Turid Vikøren, Jørn Våge, Knut Madslien, Gordon Mitchell, Glenn C. Telling, Sylvie L. Benestad, and Umberto Agrimi

https://doi.org/10.1073/pnas.2013237117

https://www.pnas.org/content/early/2020/11/18/2013237117.abstract

My brain hurts

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It’s a strange thing having your brain disappear.

Amy has encouraged me to write about it.

I’m not sure I can.

I was crying on the phone with my parents the other day, talking about how my grandfather started showing signs of Alzheimer’s at 56 (my age).

It’s emotionally complex and I’m not sure how to handle it.

But it’s happening.

I watched it in my grandfather, I know it’s happening to me.

And my 77-year old mother is going to be here in a couple of days after making a 30-hour flight half-way around the world to see her sick son.

More Brits could still die from human form of mad cow disease

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More Brits could be affected by mad cow disease as experts warn many could be infected without knowing. A second wave of deaths related to eating beef contaminated with Bovine Spongiform Encephalopathy (BSE) – or mad cow disease – could sweep the UK.

In 1993 Britain’s worst food scandal saw 4.4 million cows culled and claiming the lives of 177 people who had developed the human form of it, called Creutzfeldt-Jakob disease (vCJD). Since then, strict controls have been in place to prevent BSE contaminating food products and the use of meat and bone mix is illegal. But humans could be affected for up to 50 years, warn experts. Neurology professor, Richard Knight, of Edinburgh’s CJD Surveillance Unit, told a BBC investigation – airing July 11 – that it is still unclear how many could be affected. He said: ‘There is still so much uncertainty about this disease.

‘And one of the things that is uncertain is how many people in the UK are silently infected. ‘At the moment I have to say we are simply not sure, but every prediction suggests there are going to be further cases.’ vCJD is caused by prions, which are infectious agents made up mainly of proteins. A study of a similar disease in 2009, caused by prions, showed the disease may incubate undetected for much longer. All affected had carried the same MM genetic makeup, but in 2009 victim Grant Goodwin, 30, became the first person to die of vCJD, despite carrying the different gene type of MV. In 2014, a British man, 36, became the second MV carrier to die from the disease.

BU researchers define possible molecular pathway for neurodegeneration in prion diseases

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BU researchers define possible molecular pathway for neurodegeneration in prion diseases

https://www.eurekalert.org/pub_releases/2018-09/buso-brd092118.php

I wonder about prion diseases because I watched my grandfather degenerate from Alzheimers, and carried my suicidal grandmother into the Barrie, Ontario (that’s in Canada) hospital when I was 20 (that’s her, right, when I was a kid)

It sucked, and has scared me for 35 years.

But after years of therapy, I may be learning to deal with it.

My first book in 1997 was called Mad Cows and Mothers Milk for a reason.

A very personal reason.

A new study has shed light on the mechanisms underlying the progression of prion diseases and identified a potential target for treatment.

Prion diseases are a group of fatal neurological disorders that includes Creutzfeldt-Jakob disease and bovine spongiform encephalopathy (“mad cow disease”). They are caused by the spread of “prions”, which are altered forms of normal cellular proteins. These abnormal molecules then interact with normal proteins to promote misfolding. While we understand that this process of converting normal to abnormal protein is what causes the symptoms of prion disease (including rapidly progressive dementia, seizures and personality changes), the exact mechanism of damage to the neuronal connections in the brain and spinal cord has been poorly understood.

Researchers from Boston University School of Medicine (BUSM) used a method they previously described for culturing nerve cells from the hippocampal region of the brain, and then exposing them to prions, to illustrate the damage to nerve cell connections usually seen in these diseases. They then added a number of different chemical compounds with known inhibitory effects on cellular responses to stressful stimuli, with the objective of identifying which pathways may be involved.

They found that inhibition of p38 MAPKα (an enzyme that typically responds to stress, such as ultraviolet radiation and heat shock) prevented injury to nerve connections and promoted recovery from the initial damage. Hippocampal nerve cells that had a mutation preventing normal function of p38 MAPKα were also protected, seeming to confirm the role the enzyme plays in this disease process.

David. A. Harris, MD, PhD, professor and chair of the Department of Biochemistry at Boston University School of Medicine and corresponding author of the study, sees these findings as a major breakthrough in trying to understand and treat these diseases. “Our results provide new insights into the pathogenesis of prion diseases, they uncover new drug targets for treating these diseases, and they allow us to compare prion diseases to other, more common neurodegenerative disorders like Alzheimer’s disease.”

These findings appear online in PLOS Pathogens.

 

My super-smart partner and I meet: Prion disease in Algerian camels

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Amy says I shouldn’t cut-and-paste so much and that I’m better when I just write my own stuff.

Howard Stern’s wife said that to him, at least according to the movie version in Private Parts, 1997, but I counter with I only cut-and-paste the really interesting stuff.

Algeria, French and prions, we’re in a zone.

Everyone else is recall.net, where the copy is provided by 100K-a-year hacks who write and vomit press releases.

Journalism used to be a viable activity.

No worries, story-telling about the Tom-Wolfe-styled-vanities of the food safety privileged retain currency. And those stories are what I have been working on,

I’ll go with a Paul Giamatti,-style, who I am enjoying in Billions and was great in John Adams, Cinderella Man, American Splendor, and so on.

Everyone needs a Paul.

Or an Amy.

Her accomplishments over the seven years since we moved to Australia, including caretaking me and Sorenne, have been extraordinary.

Much love.

Prion disease in Dromedary camels, Algeria

6 June 2018

Emerging Infectious Diseases Vol 24, no 6

Baaissa Babelhadj, Michele Angelo Di Bari, Laura Pirisinu, Barbara Chiappini, Semir Bechir Suheil Gaouar, Geraldina Riccardi, Stefano Marcon, Umberto Agrimi, Romolo Nonno, and Gabriele Vaccari

https://wwwnc.cdc.gov/eid/article/24/6/17-2007_article

Prions cause fatal and transmissible neurodegenerative diseases, including Creutzfeldt-Jakob disease in humans, scrapie in small ruminants, and bovine spongiform encephalopathy (BSE).

After the BSE epidemic, and the associated human infections, began in 1996 in the United Kingdom, general concerns have been raised about animal prions.

We detected a prion disease in dromedary camels (Camelus dromedarius) in Algeria. Symptoms suggesting prion disease occurred in 3.1% of dromedaries brought for slaughter to Ouargla abattoir in 2015–2016. We confirmed diagnosis by detecting pathognomonic neurodegeneration and disease-specific prion protein (PrPSc) in brain tissues from 3 symptomatic animals.

Prion detection in lymphoid tissues is suggestive of the infectious nature of the disease. PrPSc biochemical characterization showed differences with BSE and scrapie.

Our identification of this prion disease in a geographically widespread livestock species requires urgent enforcement of surveillance and assessment of the potential risks to human and animal health.

 

 

Wow: Grass plants can transport infectious prions

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Grass plants can bind, uptake and transport infectious prions, according to researchers at The University of Texas Health Science Center at Houston (UTHealth). The research was published online in the latest issue of Cell Reports.

prion.plants.may.15Prions are the protein-based infectious agents responsible for a group of diseases called transmissible spongiform encephalopathy, which includes bovine spongiform encephalopathy (mad cow disease) in cattle, scrapie in sheep, variant Creutzfeldt-Jakob disease in humans and chronic wasting disease (CWD) in deer, elk and moose. All are fatal brain diseases with incubation periods that last years.

CWD, first diagnosed in mule deer in Colorado in the late 1960s, has spread across the country into 22 states, according to the Centers for Disease Control and Prevention (CDC), including the counties of El Paso and Hudspeth in Texas. In northeastern Colorado and southeastern Wyoming, the disease is endemic. Soto’s team sought to find out why.

“There is no proof of transmission from wild animals and plants to humans,” said lead author Claudio Soto, Ph.D., professor of neurology at UTHealth Medical School and director of the UTHealth George and Cynthia W. Mitchell Center for Alzheimer’s Disease and Other Brain Related Illnesses. “But it’s a possibility that needs to be explored and people need to be aware of it. Prions have a long incubation period.”

Soto’s team analyzed the retention of infectious prion protein and infectivity in wheat grass roots and leaves incubated with prion-contaminated brain material and discovered that even highly diluted amounts can bind to the roots and leaves. When the wheat grass was consumed by hamsters, the animals were infected with the disease. The team also learned that infectious prion proteins could be detected in plants exposed to urine and feces from prion-infected hamsters and deer.

Researchers also found that plants can uptake prions from contaminated soil and transport them to different parts of the plant, which can act as a carrier of infectivity. This suggests that plants may play an important role in environmental prion contamination and the horizontal transmission of the disease.

To minimize the risk of exposure to CWD, the CDC recommends that people avoid eating meat from deer and elk that look sick or test positive for CWD. Hunters who field-dress deer in an affected area should wear gloves and minimize handling of the brain and spinal cord tissues.

“This research was done in experimental conditions in the lab,” Soto said of the next step. “We’re moving the research into environmental contamination now.”

First author of the paper, “Grass Plants Bind, Retain, Uptake and Transport Infectious Prions,” is post-doctoral researcher Sandra Pritzkow, Ph.D. Co-authors from UTHealth are Rodrigo Morales, Ph.D.; Fabio Moda, Ph.D.; and Uffaf Khan. Co-authors from the Prion Research Center at the College of Veterinary Medicine and Biomedical Sciences, Colorado State University, are Glenn C. Telling, Ph.D.; and Edward Hoover, D.V.M., Ph.D.

Stanley Prusiner: a victory lap for a heretical neurologist

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Abigail Zuger of the New York Times writes that sweet revenge comes in many delectable forms, among them the receipt of accolades for work long scorned. And then to get to tell the whole story at length and without a single interruption — small wonder that the Nobel laureate Dr. Stanley B. Prusiner, a renowned neurologist at the University of California, San Francisco, writes with a cheerful bounce. Once disparaged, his scientific work is now hailed as visionary, and his memoir takes the reader on a leisurely and immensely readable victory lap from then to now.

PRUSINERIn the process, two stories unfold. The first is the progress of Dr. Prusiner’s thinking on the transmissible proteins he named prions (PREE-ons) in 1982, starting with his first experiments on an obscure disease of sheep and ending with the most recent work linking prions to an array of human neurological catastrophes, including Alzheimer’s disease. The science is convoluted, like the proteins, and for the uninitiated the best way to achieve a rudimentary grasp of the subject is to hear it the way Dr. Prusiner tells it, from the very beginning.

But a parallel narrative turns out to be equally fascinating: perhaps not since James D. Watson’s 1968 memoir “The Double Helix“ has the down and dirty business of world-class science been given such an airing. Dr. Watson raised eyebrows with his gossipy account of the serious task of unraveling the genetic code — and he was working in genteel postwar Britain at the time, with experimental science still at least in theory a gentleman’s game. That illusion is long gone: The stakes are considerably higher now, the competition fierce, the pace frantic, and Dr. Prusiner, 71, revisits quite a few of the battles that punctuated his long research career.