352 - Prions and Chronic Wasting Disease
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Kevin Folta: [00:00:00] Hi everybody. And welcome to this week's podcast. This week. We're speaking with Dr. Sandra PSCO. She's an assistant professor with the Mitchell center for Alzheimer's disease and brain disorders at the McGovern medical school at the university of Texas health Houston. So welcome to the podcast Dr. PSCO.

Sandra Pritzkow: Yeah. Thank you so much for the invitation. Um, like I'm happy to, um, talk to you today. 

Kevin Folta: Yeah. I'm happy to talk to you too. PreOn have been a kind of a hobby for a long time. it's a topic that I really am interested in because there are very unusual type of pathology or infectious agent. So if you catch a virus, you know, you're catching a virus from the environment or from somebody else, a PreOn is a molecule or a protein within ourselves.

And we already make this protein as part of our central nervous system. And the problem is, is that it changes to become pathological. And I'll let you take it from there, but let's start out with this idea of what [00:01:00] exactly is a PreOn. 

Sandra Pritzkow: Okay. Like a PreOn is an infectious agent of PreOn disease. It, um, is a misfolded version of, um, cell protein.

We all have, um, called the PreOn protein. So, um, the, the term PreOn, um, goes back to stain a prisoner and frozen and refer to a protein, being the Soly infectious. 

Kevin Folta: Okay. So this is an infectious agent that causes a number of devastating diseases in humans and other animals. But it's something that comes from within, right?

I mean, this is a cellular protein that's normally present in the number of different cells in the body. And when it converts because of either some sort of environmental or other type of genetic situation becomes a basis of pathology, is that correct?

Sandra Pritzkow: like, like a PreOn is, is more, um, only referred to the infectious agent. So the [00:02:00] misfold version. So the other one is a PreOn protein in the cell protein in which our body manufacture. So yes, there are, um, different causes, um, which can trigger the disease. Uh, like it can, um, are those three, uh, different origins, three different origins.

One origin is, um, etic. So, um, the protein can actually, um, or the gene, which coats for the protein can have a mutation. And these, um, amino as acid change can trigger the protein to have a higher propensity to, to miss for, and, um, become the, uh, infectious, um, Like misfold a version of the, the PreOn protein and this then, um, triggers, um, other CEL protein to, um, also, um, miss for and starts the cascade of, um, of the PreOn replication and the PreOn disease.

Um, like another [00:03:00] origin is through infection. So, um, that meaning that, um, We are, uptaking the, um, misfolded version of the PreOn protein inside of our body. And, um, these misfolded protein also trigger us again, cellular our protein to, um, also change the shape, change the form and, uh, misfold and start then again, the cascade of, um, PreOn replication and then the disease.

So the third possible origin is, um, actually spontaneous. So as you already said that, uh, maybe environmental changes. Um, can cause, um, uh, like a spontaneous, um, change, um, from the change, the cellular preowned protein to become the misfolded version of the preowned protein. So we don't know exactly how this happens or has as like with unknown cause.

But, um, yeah, it just happens spontaneous. So 

Kevin Folta: there's a spontaneous [00:04:00] conversion of a normal protein, which is present in ourselves to this pathological form. Okay. So what are some of the diseases that people may have heard of, or probably didn't hear? What are some of the common diseases that are associated with PreOn based conversion?

Sandra Pritzkow: So, yes. Um, it's exactly correct. How you said that there's a cellular, um, form of, um, The, the pre protein, which, um, has like normal function. And, uh, then there is this MIS foal form of the, the cellar protein, which causes the disease. Um, So, yes, as you said, there are, um, like we know an PreOn diseases and human PreOn diseases, um, like a very prominent PreOn disease is, um, actually mad cow disease.

Maybe you have heard about this. Um, cause this was like a big problem in the eighties. Um, it was affecting a lot of, um, cows and, um, there are, um, the human version of preowned diseases, like the most common one. [00:05:00] Quite for Jacob disease. Um, as you already said, this is like a very rare disease. However, um, there is concerned that, um, Any met diseases can be transmitted to humans.

So like in the case of BSE being transmitted, um, to, um, to, to humans and forming the new variant of quad disease, yes. 

Kevin Folta: Most people remember this from the eighties. So BSE is bun bovine, sponge form, and pathy, which was the. Cal version of a PreOn related disease that then could be transmitted to humans and cause a number of different pathologies.

So you mentioned the variance of crits fault GI outcome disease, but there's also other things like fatal familial insomnia and other types of diseases, neurological diseases. Is that correct? 

Sandra Pritzkow: Yes. Um, the BSS PON form, uh, the bovine spongiform disease and. Um, it was transmitted to M to humans and, uh, caused a new ran of cor disease.

But yes, you're [00:06:00] correct. There are other form of Preem diseases and humans like the familiar, um, these are more like genetic versions, but they're also, um, some pre diseases cause actually by cannibalism. Um, 

Kevin Folta: it's cool. Yeah. Kuru is kind of the cool one. It was ritualistic cannibalism that, uh, fur really was where these PreOn related diseases were first identified and be shown to be connected, to consumption of neurological tissue.

And so this was a really interesting story. Do you wanna spend a second and maybe drill down on that just a little bit. 

Sandra Pritzkow: Uh, yes, it was mostly, um, in, in, in, in kids and also in, in, um, women because, um, they were eating the brain as though, um, it goes back to like a ritual when, um, like, uh, one of the relatives dies, um, so that the person can continue living.

There are, um, eating the brain. So, and the women were mostly, um, like preparing, um, the food. So, so by preparing, maybe they had some [00:07:00] injuries in the hands, so the disease got transmitted and also, um, yeah, they were eating the brain. 

Kevin Folta: Yeah. So consumption of the brain, it's kind of a strange metaphor for the disease itself because it, it spreads by others who are consuming.

The, uh, the PreOn, which is, which is converted. So this is interesting stuff from humans, but I really wanted to talk to you because this has been over the last several decades showing up in deer, in elk and O in other types of, uh, animals and is responsible for something called chronic wasting disease.

So can you give us more of a background on what this specific pathology is? Maybe even where we see it. 

Sandra Pritzkow: Yes. So, um, chronic vine disease is a, um, pre-owned disease in, um, Sevi. Um, it affects, um, different species of, of Sevi, um, like, um, has been reported, um, wild [00:08:00] ideas, but also, um, MOS and egg mul deer, um, uh, this, um, Uh, has been, um, like spreading, like, um, extensively in the last, um, like decade.

Um, and it's becoming like a, a problem in the United States, especially, but also there have been cases reported in Europe and, um, Korea, 

Kevin Folta: and, and it seems to be getting worse and worse. What are some of the symptoms that may be observed when we look at a case of chronic wasting disease? 

Sandra Pritzkow: ah, yes. Um, so the symptoms is like, um, the animals show like a, a, a wasted appearance.

Um, and, um, why we know that actually chronic racing disease is a PreOn disease is, um, PreOn diseases have like some certain key features. So, um, like we know that, um, all preowned diseases are like fatal diseases. So, um, then also. The brain [00:09:00] becomes like a sponge. So, um, like the brain, um, gets ho, um, and it's called like spongy form degeneration.

So it looks like a, like a sponge and also you find, um, accumulation of the pre protein in the brain. So therefore, um, the people knew that, um, That chronic, uh, racing disease is also pre-owned disease because this actually, um, displays all these common features of pre-owned 

Kevin Folta: disease. Yeah. But there's one feature that it doesn.

Display. And so we in humans and in other animals, we see the propagation of this from the consumption of neurological tissue, but deer are vegetarians, I think so. So they're not eating the central nervous system tissue of other, other CVIS, right? I mean, how is this spreading in these animals? 

Sandra Pritzkow: Yes, this is a very good question.

Yes, Herbo. So they don't eat a meat. So, yes. So there are, um, three possible routes of, um, transmission. [00:10:00] Um, one is, um, like vertical from, um, the mother to the offspring. Um, another possible, um, route is, um, horizontal from man to man maybe during a mating season. Mating. And, um, I think the, probably most common in my opinion, um, transmission route is, um, through the environment.

So, um, and in fact, the deer, um, sheds pre-owned continuously through, um, like urine, um, saliva, FES, but also, um, car of, um, diseased animals, um, release pre and food environ. And, um, we, we know that pre, um, efficiently bind to soil and other environmental compounds and get accumulated. They can also get acclimated in plans.

And then, um, noninfected deers, um, like are exposed to these environment infected environment. And maybe also eat these plants and then [00:11:00] they get, um, infected. 

Kevin Folta: Well, this is a freaky new one on me because I always thought, as long as you didn't eat brains and spinal cords, you were safe from a PreOn based disease.

But what you're telling me is that this stuff is released in urine and cadaver breakdown, whatever, and actually accumulates in the environment and can be a threat to propagating PreOn. 

Sandra Pritzkow: yes. Umalthough like we have shown it depends on, um, on the pre-owned disease. Some pre-owned diseases are more, um, like based in the brain, but, um, like other pre-owned diseases, um, Chronic facing disease are also very present in the periphery.

So therefore we find that in, um, in urine and saliva and, and all like bodily 

Kevin Folta: fluids. This is really shocking because it always seemed to me that this couldn't happen. So you're telling me that if you have the right test, that you can go out like the right sensitive enough test that you could go out and survey soil or survey.

And find [00:12:00] the converted pathological form of the preowned protein in the environment? 

Sandra Pritzkow: Uh, yes. Um, I'm like we have shown, um, that, um, we have, um, experimentally, um, Exposed environmental, um, surfaces with PreOn and then we, we show them you can, um, test, um, for, with, um, with a sensitive amplification take, 

Kevin Folta: uh, technique.

that's really scary because these diseases can be kind of difficult to spot. I mean, chronic wasting in its in its full form has some symptoms, but PreOn disease. By characteristic tend to have very long latency periods. So is this also the case with chronic wasting disease and how it's affecting these different servant 

Sandra Pritzkow: species?

Yes. Um, there are automatic, um, like stats and asmatic because pre disease takes a long time to, to accumulate. Um, and, [00:13:00] um, during this time to this, this automatic phase, um, They are already pre UNS, she into the environment. So there are like maybe a lot of MD running around, which look completely normal.

But, um, they're already infected, um, and, um, spread, um, spreading the 

Kevin Folta: disease. so we, but we know that you can spread the disease from servant to servant, you know, dear to elk, dear, to moose, moose, to dear all that stuff. But it would seem as though that if this was being transmitted to humans, there would be some very clear epidemiological evidence because there's specific communities where consumption of deer and handling deer is much more common.

Is there any evidence of that? So, 

Sandra Pritzkow: um, this question, um, does not have really the definite answer. So, um, it's still under investigation. Um, like, yeah, obviously we cannot, um, infect, um, a humans. So therefore we have to use models. So, um, in the past, um, people [00:14:00] have used, um, mice, um, transgenic mice, which, um, express a human protein in this.

Um, they infected this tr mice with, uh, chronic racing disease. Um, Uh, the resides were very negative, so there was no, um, possible transmission. Um, however, then they also have used, um, other models, um, monkeys, so monkeys are closer to humans, so that's why it's a more relevant model. So they have used two different monkey species, um, to, um, analyze or to, um, investigate, um, Like a zoonotic potential of chronic racing disease.

One of them is, um, the screw monkeys and, uh, SC monkeys showed that they're highly susceptible to acquire, um, pre-owned disease. Whereas, um, the Mahas, um, showed contr results. One group reported, um, like a negative result. So they did not see trans. And, um, another group, [00:15:00] um, showed, um, evidence that actually, um, chronic racing disease can be transmitted to CCAs and maybe have a tic potential to humans.

Kevin Folta: And so when you're saying transmissible, what you're saying is, is that the introduction of the misfolded protein has the ability to influence the. Protein resident cellular protein and convert it to this pathological form. And so is that the correct interpretation? 

Sandra Pritzkow: Yeah. Transmittable means, um, that, um, yes, transmittable means that, um, It can, um, yes.

Change the confirmation of the cellular protein. So, uh, to become a misfold version, that's correct. 

Kevin Folta: Well, I, I should have asked this earlier, but what does the normal cellular PreOn protein do? You know? What's its role it's role. Can't be to be a target for misfolding to cause some sort of weird disease.

Sandra Pritzkow: yeah, like Aon, actually the, [00:16:00] the real function of the PreOn protein. However, there have been, um, like some function proposed, for example, um, that it maybe play a role in the violation of the accents, or it may, um, play also a role in the optic of CAPA into the sales. Um, but this is still, um, still unknown.

Um, but, um, Probably the function of the, um, cellar pre protein is not essential because there are, um, experimentally created animals, which do not carry the cellar pre protein. And they, um, do not show obvious changes. They look, um, pretty, no, 

Kevin Folta: yeah, pretty normal. I remember the old papers back in the 1990s where they made knockout mice and the knockout mice looked pretty much normal.

The only thing they did weird was that they ran on the wheel at different times than they normally would. Yeah. And so the, so [00:17:00] mice have very, uh, very strict habits about different things they do in the cage and running on the wheel is a big one. Yeah. So they, they would run at the normal time. But when the knockout ones seem to have a problem with their circadian rhythms, that they were maybe slightly altered, but I haven't really looked at the data on this in, in a couple decades.

So not terribly helpful. Um, we're speaking with Dr. Sandra PSCO, she's an assistant professor with the Mitchell center for Alzheimer's disease and brain disorders at be govern medical school at UT. Houston. This is the talking biotech podcast by collab. And we'll be back in just a moment. And now we're back on the talking biotech podcast.

We're speaking about pre ons and the relationship to chronic wasting disease. We're speaking with Dr. Sandra PSCO. She's an assistant professor at the U McGovern medical school at university of Texas health in Houston. And we're speaking about chronic wasting disease, which I think that if this thing was really zoonotic and jumping to humans, [00:18:00] that we would see it more prevalent in places where people were hunting.

It would seem like you'd have sound epidemiological evidence of this. So deer hunting is a huge sport through most of the country. So do we actually see any evidence of this, uh, from epidemiological studies? 

Sandra Pritzkow: Yes, there have been reports, um, that there's a higher prevalence of pre disease in areas where hunters are present.

But, um, there's no real evidence, um, that this is really caused by, for example, chronic racing disease. So it can be just, um, a coincidence. Um, but up to date, there is, um, no, um, Prove that hunters, um, got infected with, um, chronic based disease. Okay. 

Kevin Folta: But what about the animals themselves? Are we seeing more and more spread of this disease among deer and other types of animals?

Because it seems to me over the last 20, 30 years that this is becoming a bigger and bigger problem in [00:19:00] spreading. Uh, 

Sandra Pritzkow: yes. Um, it has been, um, spreading, um, extremely, um, like it's growing and growing. Um, before like maybe 20 years ago, it was, um, just in like a small area of the United States. And now you can find it in, um, like half of the states of the United States.

Kevin Folta: What about Europe and other places in Asia? 

Sandra Pritzkow: Yes, you are absolutely correct. Um, we also, um, we are also reported some cases in, in Europe, in, um, in Norway, but I think also in Sweden and in Korea. 

Kevin Folta: Yeah. Can we learn anything from a leic variation, like different versions that maybe have a higher propensity for conversion to the pathological form from the cellular form?

Sandra Pritzkow: So what, there are investigate. There are, um, evidence. That there are also, um, different strains, um, of, of chronic racing disease, which do have, um, a different, um, like there may be [00:20:00] more infectious or they're actually able to, um, to, um, transmit, um, to other species and then become like a zoonotic pretension.

Kevin Folta: Well, what is exactly being done to eradicate chronic wasting disease? 

Sandra Pritzkow: It's like, uh, uh, there are, um, some, um, strategies as of, one of them is like, um, surveillance, just monitor, um, uh, the areas which are infected, um, with cor disease. Um, another approach is that, um, when they are, um, Like a farm reporting, um, infectious, um, deers, um, like an agency comes and they are depopulating, um, the farm and they are decon contaminating the area.

Um, however, I think that, um, this is not enough, um, to eradicate the disease because chronic racing disease is also spreading a lot in the wild. So, [00:21:00] um, there, that's why it's difficult to get this under control. But, um, in my opinion, uh, what would be probably good to, uh, to develop a vaccine, um, which, um, can prevent the disease or, um, also, um, combine this with, um, routine testing, um, And then depopulating, uh, affected deals.

Kevin Folta: Uh, so rather than depopulation couldn't, they just use vaccination. It seems like you'd be able to design a vaccine that would work against specific alleles, like, you know, mRNA vaccines, or even, um, a, a vaccine against the misfolded form, you know, using that, uh, the epitopes presented by the misfolded form of the protein, but there's probably not a lot of, uh, interest or dollars in this kind of thing.

So am I just being overly Cyn? 

Sandra Pritzkow: the farmers are maybe, uh, more interested in, um, the, the, um, vaccine get developed because they're losing a lot of money actually, when, um, [00:22:00] when they're losing the whole existence. And they're getting a little bit of money back from the, um, from the government, but, um, they're losing the whole existence when the whole farm gets de.

So, um, and the farmers, they do have, um, half a lot of money. So that's why this could, um, potentially be, um, developed by, by money given by from 

Kevin Folta: farmers. Yeah. And most people don't realize that deer are farmed as livestock, that either directly for venison production or also to populate, uh, deer parks for hunters, where they can go hunt inside a fenced in area, kinda like, you know, a game reserve, that kind of thing.

Sandra Pritzkow: Uh, yes, there are, um, farms and I, I think it's for, um, like meat production, but also for, for hunting. So yeah. Um, there are pro producing deers and so that people can go and, and hunt them. 

Kevin Folta: Okay. So mitigation, you know, maybe, uh, maybe something we need to concentrate more on, but in terms [00:23:00] of the research that you're doing, where can people learn more about chronic wasting disease?

Um, the, the PreOn diseases and the work that's being done inside your program? 

Sandra Pritzkow: Yes. If, if you want to learn more about, um, um, our lab and about chronic racing disease, um, we have a Twitter account, um, it's called, um, the. Miss foing, um, disorder laboratory at the mega fund medical medical school in Houston where we post, um, updates and, and research.

Kevin Folta: Yeah. So for those who are interested in Twitter, it is at McGovern med at MC G O V E R N M E. D, and you can follow that. They frequently have updates from the protein folding lab group. So Dr. Sandra PSCO, thank you very much for joining me today and best wishes in your research going forward. 

Sandra Pritzkow: Yeah. Thank you so much.

Um, it was a pleasure talking to you. 

Kevin Folta: And to all the listeners. Thank you very much for listening to another episode of the [00:24:00] talking biotech podcast. Please keep writing those reviews and tell a friend, uh, the area of PreOn research, especially as it applies to these easily transmissible zoonotic types is really intriguing.

It's a really interesting area of biology and interesting area of medicine and something that just about anybody can really find interest in it. It's a great way to cultivate new interest in biology and new interest in biotechnology. This is a talking biotech podcast. And we'll talk to you again next week.