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Significant breakthrough in search for Parkinson's biomarker (michaeljfox.org)
495 points by sandGorgon on May 1, 2023 | hide | past | favorite | 185 comments



For those living in the bay area, you should know that the groundwater in many areas is contaminated with TCE due to computer manufacturing industry which used it as a solvent. Dry cleaners are another common culprit of contamination to the groundwater. These groundwater plumes can extend for quite a large distance from the original site of contamination and seep into the first story of residences and buildings through vapor intrusion. The TCE solvent is directly linked to Parkinsons [1].

Take a look at where you live on the California waterboard website [2] and look for nearby groundwater contamination sites. TCE / PCE contamination sites anywhere near your residence or workplace would put you at risk of getting Parkinsons. I know someone who got it and indeed they lived near a dry-cleaner that was leaching TCE into the groundwater decades ago. The solvent entires your residence through vapor intrusion, especially on the first floor or basement.

[1] https://www.urmc.rochester.edu/news/story/common-dry-cleanin...

[2] https://geotracker.waterboards.ca.gov/map/?CMD=runreport&mya...


This Twitter thread on the specifics of how dry cleaning retail stores contribute to the problem is an excellent quick overview:

https://twitter.com/realEstateTrent/status/14378028033139220...


Seems sensationalist


It doesn't seem sensationalist to me. I looked up three different strip malls that I am familiar with and all of them have some kind of PCE cleanup sites from previous or current dry-cleaners.

Here's one example in Santa Clara of a dry cleaner that operated in the 60's and there has been an active remediation project to cleanup the groundwater that has been on-going to this day [1]. In this case a single dry-cleaner which operated decades ago contaminated the water table and the chemicals flowed to neighborhoods even across the street. There is an extensive record of cleanup actions being taken on a nearly monthly basis going years back, including continuous well monitoring and soil vapor intrusion investigation. The map that was sent out to residents shows the extent of how far the ground water plume reaches, it's stunning to see how far one spill can go depending on the water table [2].

There are open remediation cases like this in almost every strip mall across America. This is a widespread problem and most people just aren't aware of the extent of it.

[1] https://geotracker.waterboards.ca.gov/profile_report?global_...

[2] https://documents.geotracker.waterboards.ca.gov/regulators/d...


The Twitter thread says a single shot glass of the stuff will contaminate a site "forever". That's not even true for weapons grade plutonium.


I don't follow. What does plutonium have to do with this chemical?


What can I do if I live near one of the red spots? Do air and water filters help?


If you’re in an apartment building, moving to a higher floor would help as it affects the basement and first floor the most.

If you’re in a house, the same mitigations for radon exposure would likely work to reduce TCE as well.

Regularly ventilating your home may also help keep the levels down.

Lastly, there are typically many years of exposure required before you notice any symptoms. So moving would be another viable option.


Open the windows or move. Your tap water is unaffected, you'd have to be on a well to be impacted. But activated carbon water filters work to remove it.


Why is still allowed to leach tce into groundwater


It's not supposed to leach into the groundwater, but nobody is enforcing the companies that are handling these chemicals to ensure they don't get into the groundwater supply. Many of the worst contaminations in the area were caused by big tech companies such as HP who didn't realize their underground TCE tanks were leaking whoops.

As of 2023 only two states have banned TCE (Minnesota and New York), and the federal government has yet to do anything to control it. It has and will continue to be used extensively in industrial application such as at electronic assembly lines, dry-cleaners, mechanics, air force bases, coffee decaffeination, textile industry, and the list goes on. The best you can do is live in a highly residential area which is far from the locations where any of these business could operate.


It's not allowed. These are old plumes and they stay around for a long time and are very expensive to clean up.


Cool, let’s make the companies that caused it pay for it


That's why we have the EPA Superfund program

https://en.wikipedia.org/w/index.php?title=Superfund


It should be renamed "minifund" given how small the fund is today and how few sites they actually clean up

The reinstatement of the excise tax in 2022 may actually be harmful to its own environment. It's an import tax on crude oil, which will encourage the domestic oil industry leading to an importing of pollution.


It's clearly not doing its job well, there are still constant ecological disasters that never get properly addressed.


There are a lot of superfund sites, man. And it sucks that the FeddyGov is on the hook to cleanup the mess that big corps make.


Santa Clara county has the most superfund sites.


That's clearly socialism and making companies pay for damage they cause and their externalaties is oppressive regulation. We should instead reduce the EPA's power until they are a shell of an organization. How else are we going to get our burning rivers back?


Many of those companies no longer exist...


If anyone wants to help the cause, PPMI is a large scale study funded by the Michael J Fox Foundation to help find early biomarkers.

Even if you have no history of Parkinson’s in your family, you can participate in the study which is primarily surveys. It's easy to participate, and can help find more early indications of a horrible disease.

https://www.michaeljfox.org/ppmi-clinical-study


Unfortunately US and Canada residents only for now.


Appears to be US only right now.


Had to start researching this when a family member was recently diagnosed.

Parkinson's has many forms and many causes. There's a big divide between Parkinson's _disease_ (idiopathic Parkinson's) and Parkinsonism from a variety of sources - stroke, drug-induced, and so on. There are also other conditions, like progressive supranuclear palsy, that are considered either to masquerade as Parkinsonism or to constitute another cause of Parkinsonism.

Recommended treatments differ by the root cause of the symptoms. Some of the treatments that are recommended for one form may be contraindicated for other forms, or for different stages. For example, the recommended dopamine agonists are also the primary cause of Parkinson's hallucinations, so you have to trade back some strength and mobility if those start.

Something like 80% of Parkinsonism derives from idiopathic Parkinson's Disease.

Overall, it feels like we're really just getting started on these conditions. For decades, it's been thought to be primarily a motor disorder, but it turns out that there are scads of cognitive symptoms that develop years earlier than motor symptoms.


> Parkinson's has many forms and many causes.

A lot of my family were farmers. I've had close relatives die with severe Parkinsons, primarily those that farmed their whole life. Their theory was that it was really exposure to a lot of toxic farm chemicals. I can imagine Parkinsons turning out to be several different conditions with similar symptoms.


My grandmother had 10 siblings. They grew up farming and they picked cotton every summer. Of the 11 siblings, I believe 8 of them have parkinsons. They have long thought exposure to whatever pesticides were used on the cotton may have caused the parkinson's late in life. I believe the siblings that don't have parkinsons were those that for whatever reason, had much less exposure to the cotton. Both parents lived pretty long and neither had the disease. There are two sets of twins, one identical, one fraternal. I'm not sure which of those have it. I've long thought that a case study could be made just about that family of 13.


In The Netherlands we have A LOT of farmers with parkinsons. Most, if not all cases seem to be related to Roundup/Glyphosate.


I wonder how much of this gets "downstream" to people eating the food produced.

EDIT: https://www.ewg.org/foodnews/summary.php

The 2023 DIRTY DOZEN

Of the 46 items included in our analysis, these 12 fruits and vegetables were most contaminated with pesticides:

    Strawberries
    Spinach
    Kale, collard and mustard greens
    Peaches
    Pears
    Nectarines
    Apples
    Grapes
    Bell and hot peppers
    Cherries
    Blueberries
    Green beans


The carnivore doesn't sound so idiotic viewed under that lens. The thing about mammals is that they have liver and kidneys, which are remarkably good at filtering toxins. Certainly much better than a plant.

I wonder if the reason many feel better eating only meat is that they avoid pesticides that wreck havoc on their body. I know I do feel like a million bucks after just 10 days, even though it's extremely boring.


On the flip side is bioaccumulation, in which contaminants and toxins are concentrated in organic material, particularly animals, and most especially for predators-of-predators.

The reasons for high mercury levels in tuna, shark, and swordfish is that each of these is both a predator and often eats other predatory species. There are numerous other examples of both species and contaminants, including even natural and even vital substances, e.g., vitamin A toxicity in carnivorous livers.

<https://en.wikipedia.org/wiki/Bioaccumulation>


That's a good point, though we (humans) tend to eat only herbivores and not many carnivores/predators, probably because of that reason. I can't think of any actually, apart from fish.


The reason has far more to do with metabolic efficiency of conversion of biomass into food than with bioaccumulation --- you'll see roughly a 10-fold drop in food production at each trophic level. There are exceptions amongst hunter and trapper cultures, though even there herbivores are generally more abundant than carnivores, and are less treacherous to hunt. You will find ominvores occasionally included in diets: bear, racoon, and members of the rodent family on occasion.

Fish (amongst other sea life) are an exception specifically because humans aren't concerned with that efficiency, and carnivorous fish tend to grow larger which poses efficiency benefits when line- or net-fishing.

Another class is birds, notably fish-eating species, which may be 2nd- or 3rd-order carnivores (carnivores of carnivores, or carnivores of carnivore-eating carnivores).


Personally, I'm much more concerned about the risks to farm workers than risks to the general population.


Roundup/Glyphosate is such a nasty chemical. Farmers use it in practice regularly for crop desiccation [1] in order to yield more harvest cycles. Why do we still allow it knowing what we know?

[1] https://en.wikipedia.org/wiki/Crop_desiccation


Because cash rules everything around me ("CREAM"), aka dolla dolla bill yall.

Or to put it another way, roundup is made by a large, influential company (Monsanto) and they can pressure regulatory agencies & politicians.


Monsanto is big money, that's why. Just like everything else in our blown out civilization.


Certain pesticides are confirmed causes of Parkinsons. Don't remember which now, but could look it up.


There are actually a number of different pesticides that are linked to parkinson's. It's especially strong for farmers who get a much larger dose than the people consuming the food - simply type "parkinson's farmer pesticide" into google scholar. One example is Paraquat, which is already banned in numerous countries but not US [1]. Aside from this Parkinson's link being established in farmers who use Paraquat, it's found it rats too.

Another is rotenone [2].

https://en.wikipedia.org/wiki/Paraquat https://en.wikipedia.org/wiki/rotenone


No, none are "confirmed causes". There are mild associations between the use of certain pesticides and Parkinson's, but much lower than the overall genetic risk factors, and there's always the possibility of confounding factors in the studies.


What's your source, if you don't mind me asking? I ask because some pesticides are well established to be linked to increased risk of parkinson's. Including carbamates (3.5x), organophosphorus (2x) and organoclorine (2x).

https://pubmed.ncbi.nlm.nih.gov/33991619/


Maybe. The correlation is weak. If you're looking for a stronger correlation, try obesity.

People who are very overweight or obese in middle age (35-55) are significantly more likely to develop Parkinson's after 60, even if they lose the weight prior to diagnosis. Now this could be a pure lifestyle-correlation, but my spidey sense suggests it's causative, knowing how causative obesity is for SO MANY other degenerative and chronic diseases.

The best advice you can give anyone, at any time, for the prevention of nearly every poor health outcome we have a name for is and always will be: don't get fat; if you're fat, stop being fat.


My father, an agricultural engineer who worked with herbicides and pesticides for some 30 years, passed away a few days ago from advanced Parkinson's at the age of 82. Now he wasn't exactly in his teens anymore but his 87 years old brother who was a teacher is in fairly good shape for his age while my father became a ghost of a man (in end stage you cannot even swallow anymore).


Is this a consequence of the 'woman who can smell Parkinson's'?

https://www.parkinsons.org.uk/news/meet-woman-who-can-smell-...


Interesting that big flu outbreaks cause a long term spike in Parkinson's - how much more will be traced back to the impact of viruses?

Saw that come up as a worry around Covid, seems the loss of smell/taste is a commonality with Parkison. We will not know for a decade or two though, but these biomarkers might help accelerate measuring the impact.


It’s very plausible in 10-20 years or so. Studies found a massive increase in acting out of dreams amongst those who had Covid.

This acting out of dreams is a very strong precursor to Parkinson’s. According to this, 80% of people with it get Parkinson’s within 20 years.

https://www.salon.com/2023/04/24/long-parkinsons/


Well that certainly puts a dark twist on the phrase "living the dream".


I am currently struggling with the idea of going back to vaping, having quit 3 years ago following covid, because nicotine has consistently shown to be a strong drug for fending off parkinsons.


Do you have any sources? Or did you mean that ironically, because as a smoker you die earlier than the average gets Parkinson's?


It's well established that nicotine fends off parkinsons (but won't do anything if started when sympoms appear)

https://scholar.google.com/scholar?hl=en&as_sdt=0%2C31&q=nic...


Seriously? You can't think of a more efficient use of the time and money?


Would nicotine patches help?


I could do that, but I smoked cigarettes for 7 years and then vaped for 9 years. So I don't know if I could jump back into nicotine but hold off on the smoking/vaping aspect of it.


Funny tangent, I quit vaping on 2 Jan 2020 after the worst flu I have ever had (after a flight abroad.. early COVID?) and while I was finally successful after a decade of quitting, it killed all my motivation and energy.

Then I got diagnosed with ADHD, got stimulant meds which restored the energy and then some, and it was clear I had been self medicating all my life with nicotine and I was completely lost without. If one day I lose access to stimulant meds, you better believe I'm back on the patch and/or the vape.

But in general dude, do not joke about nicotine. You are 3 years clean, it's incredibly hard to quit. If you done it once, it doesn't mean you'll do it twice. Maybe avoiding Parkinson's by vaping is a terrible excuse. You've never known addiction if you believe this time you'll be able to control it.


This is everything and nothing all at once.

Synucleinopathies are found in many neurological diseases. They even find it in Long COVID.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9108014/

This is a marker for many diseases. They still have not found the trigger for Synucleinopathies, which I believe is a nutrient deficiency causing oxidative stress and zinc is at the top of my list.

https://academic.oup.com/hmg/article/23/11/2791/621896 https://academic.oup.com/brain/article/142/8/2380/5523051

By the way, this is the same reason peop[le loose their sense of smell with COVID. And I believe COVID is going to cause a rise in Parkinson's cases.


If the loss of smell is so brief, why would it cause this later?


It might not.

If the build up of alpha-synuclein is rapid during COVID that might only cause a temporary issue if the person can still break it down. These people might not go on to get Parkinson's.

Matrix metalloproteinases break down alpha-synuclein.

https://pubmed.ncbi.nlm.nih.gov/21330369/

And it's cofactor, the metal that increases MMP3 activity is zinc (and calcium).

https://www.uniprot.org/uniprotkb/P08254/entry

This is why I keep screaming that zinc is probably a central deficiency to both of these disorders in some people.


I hope this will also help to advance the research on Lewy Bodies Dementia (also correlated by mis folded alpha synuclein


As I am now casually interested in the subject, what's a good resource to find out why this disease is hard to detect and cure and various other interesting facts?


One neglected issue in the article and the comments is that Parkinson's is associated with exposure to various neurotoxic substances including organophosphorous pesticides:

https://academic.oup.com/ije/article/42/5/1476/623189

> "In a population-based case-control study, we assessed frequency of household pesticide use for 357 cases and 807 controls... Frequent use of any household pesticide increased the odds of PD by 47% [odds ratio (OR) = 1.47, (95% confidence interval (CI): 1.13, 1.92)]; frequent use of products containing OPs increased the odds of PD more strongly by 71% [OR = 1.71, (95% CI: 1.21, 2.41)] and frequent organothiophosphate use almost doubled the odds of PD."

This is further supported by previous discoveries of Parkinson's brought on by exposure to an opiate analog MPTP, as well as several other pesticides:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5345642/

> "The identification of MPTP, a relatively simple compound which causes selective degeneration of the substantia nigra after systemic administration, has had an a significant impact on the understanding and treatment of Parkinson’s disease (PD) over the last 30 years."

It's rather curious that this foundation neglects to discuss any of this, but it is funded by entities affiliated with pharmaceutical manufacturers so perhaps it's not something they want to bring attention to? It does fit with a general pattern of attempting to blame diseases affiliated with environmental exposures on genetics, however.


I’d recommend Rory Cellan Jones on Substack [1]. He was the technology correspondent for the BBC until a few years ago - and is now retired partly because of the onset of Parkinson’s.

As a result he’s devoted much of his retirement to reporting on innovation in treating and managing Parkinson’s.

[1] https://rorycellanjones.substack.com


This might be useless to you, but OMIM is the canonical database of genetic diseases, and has tons of information:

https://www.omim.org/entry/168600

https://www.omim.org/entry/168601


A cursory browse of wikipedia is my first port of call, that's what chatgpt bases their answer on as well (what the other commenter pointed out).

Yeah it's not verified etc, but it's more accessible than reading the sources it cites itself on.


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Can we have a line on the HN guidelines saying "telling people you asked about <topic> on ChatGPT doesn't make for interesting discussion. Please refrain from doing so."

Especially in this case where you don't even tell what did you find out, only that you did ask ChatGPT. Good for you.


It's the new LMGTFY


But posing as helpful instead of sarcastic, yet equally annoying.


Why feed yourself with potential misinformation that you don’t know the true source of and you might never double check?


> Why feed yourself with potential misinformation that you don’t know the true source of and you might never double check?

Because I enjoy reading HN?


When you run out of HN, do you hit up ChatGPT?


I ask ChatGPT to write me a comment thread in the style of Hacker News.


Oh, that was just too easy... :)


As opposed to? Unless you're actually going to read individual papers, vet the authors, have the baseline statistical knowledge to understand the results, etc, you're always going to be susceptible to potential misinformation. This HN topic is a good example of the difficulty of verifying information.

Who's to say that ChatGPT doesn't provide a better job of filtering it out?


Yes, I would start with Google Scholar, or at least Wikipedia because it tries to provide sources for each statement that it makes.

> Who’s to say that ChatGPT doesn’t provide a better job of filtering it out?

No one because no one knows what sources ChatGPT is blending together in its sentences.


> I would start with Google Scholar

You actually should vet everything you read through Google Scholar too. There is a pervasive belief of consensus in academic science and unfortunately individually verifying information is the only thing we know that actually works- not political consensus.


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I am not trolling. I don’t recommend engaging in a good-faith dialogue with someone by prefacing it with your belief that they are trolling.

If you're basing your trust in ChatGPT on the claim that it is trained on Wikipedia, you might as well read Wikipedia instead because then you also see the sources for each claim, or the fact that certain claims are unsourced. ChatGPT will not let you know if a certain claim is more controversial, nor give you further sources to read if you want to know the background of a claim.


I don't have trust for things, I build trust with other humans if earned, potentially dogs. Beyond that there's no reason to trust with objectivity and reason.

Digression aside, I would impress upon you I haven't claimed, nor do I believe what you're claiming I have. I am simply providing you with a slice of the larger original academic paper that provides great, rigorous, and peer-reviewed documentation of precisely what GPT is, and what it's trained on.

From this paper you'll perhaps gather an instinct that these folks working on this problem are widely aware of the extremely well-known concept of "open source knowledge" and were well considered in their application of pruning data to their needs.

I believe you'll perhaps further gather retrospective insight upon the idea that GPT is doing anything more than giving you a T9-predictive-autotext for the entirety of that dataset; meaning you can try to coax it into saying anything you want but if the p-values aren't right or the predictive potential of a given token "coming up next" isn't there, that's just.. how it goes.

It's data. It's not quite the tower of Babel, but we'll get there soon enough. Kind of like how all the fancy 3D video game rendering software that looks incredible these days is still just manipulating tuples and vectors with matrix calculations, stuff you could do on paper but why would you do that math to describe a picture when you could just draw it.

ChatGPT is just drawing the pictures (in this poorly chosen analogy), and giving us the cool graphics. The math is all pretty benign and based in the fundamentals of neural networks, not even the more fanciful CV and deeper trained NLP can get to.

Info-scientists, I wonder what the "rainbow table" of all language and ideas etc. that would be relevant to a latent language learning model would be... this is a wonder to me because I lack the sufficient knowledge and field expertise.


Because ChatGPT assembles letters into words and sentences without attribution and so is untrustworthy.


I wonder if there is any relation to the odorous biomarker that dogs can sniff out in Parkinson’s patients: https://pubmed.ncbi.nlm.nih.gov/36054272/


First discovered by this Scottish woman being able to detect the smell herself https://www.theguardian.com/society/2022/sep/07/woman-who-ca...


My grandmother had Parkinson's and it was awful. How long until I can go to the doctor, get some blood drawn, and see if I'll develop it one day?


What would you do if you found out you would? (I ask as someone whose great-grandfather, great-uncle, and grandfather all had Parkinson’s.)

I’ve avoided any testing because, as far as I know, there’s nothing preventative to be done. I’d love to hear otherwise. I’ve broached the subject with my last two primary care physicians and both advised that there was no point in knowing.


If you know for certain, then you might do things you otherwise wouldn't.

E.g decide to have children or not, plan a will. Live life to the max. Potentially get a head start on treatment if one were ultimately available, even if super experimental and maybe even not working in the end.

Honestly, there are many reasons to know beforehand and not a lot of reasons to not know.


So if you gonna die anyways you won’t live life to the max? Probably better off not finding out and live life to the max without the thought of it


Things like deciding when to retire. You might want to retire earlier and spend time doing things instead of waiting to retire to get maximum retirement payout.


But will you really enjoy your days with that cloud over your head, if I were to choose I wouldn’t want to know


Ignorance is bliss


Parkinson’s does not prevent any of those.


Yes, the age old debate of knowing versus not knowing.

I think I’ll skip it because it’s not productive.

However, I will point out that your average billionaire with a few decades of advanced notice might be willing to fund research:

https://www.forbes.com/sites/kerryadolan/2022/12/09/exclusiv...


>What would you do if you found out you would?

There's quite a few big decisions to make, no? Preparing financially, making plans for when you're going to retire or what to do before, whether you want to have kids and put them through this, and so on.

If I found out I had a degenerative disease at the very least I'd opt for an egg or sperm donation and not delay having kids. You probably don't want to be in declining health while they're growing up.


> I'd probably opt for an egg or sperm donation

so that any kids produced would have a high probability of having the disease too?


no, so that they don't have a high probability of having a disease because I'd not be passing it on. How did you read anything else into that statement?


It could be more clear. Something like "use a donor". "Donation" can go either way (giving or receiving).


There are lifestyle factors that are supposed to slow the onset and progression. Granted most of those, like exercise, are supposed to be things we do anyways.


I think if you find out young enough you can probably try to follow a different trajectory in life. Maybe abstain from stuff like finding a partner, having kids, buying a home or saving for retirement. Make plans to end up in circumstances where you're eligible for MAID and just vibe until you're ready to use it.


Well, Michael J. Fox was diagnosed exceptionally young. Most people only suffer when they're of retired age.


Pick up a nicotine addiction.

Seriously, it has long been understood that people who smoke have dramatically lower levels of parkinsons. It comes from the neuroprotective properties of nicotine. You don't have to become a smoker, you could theoretically use any of the other forms (vape, gum, patch)


https://www.apdaparkinson.org/article/smoking-and-parkinsons...

Smoking and Nicotine addiction are still bad.


Nicotine is wonderful. 2mg and 4mg lozenges are readily available, you don't have to take up smoking to get it. It's excellent for many, many things: cognition, focus, appetite control, positive habit formation, etc.

Addiction is literally its only downside.


You don't have to smoke cigarettes to get nicotine. Using a patch just gives you nicotine in a very safe way, and nicotine itself isn't particularly harmful.


Curious if you have any links to support lower incidence of Parkinsons for smokers. I found this, which states that nicotine does not slow the disease once started: https://www.michaeljfox.org/news/nicotine-patch-not-benefici...


I'd encourage you to just search google scholar for "nicotine and parkinsons" there are dozens and dozens of studies. It's been well established for decades now, as it stood out, especially in the past, that cigarette smokers weren't developing parkinsons as expected. Here is a recent meta study though:

https://www.sciencedirect.com/science/article/abs/pii/S01674...

There have also been numerous studies that have found that starting nicotine once symptoms begin is too late, with little or no effect. It is hypothesized that there is some critical point that once crossed, nicotine no longer has an effect. Parkinsons is believed to slowly develop over years or decades, and nicotine stunts this early progression.


That's a good question. I'm not sure. But it feels like something I'd want to either prepare myself for or just have the relief it won't happen to me.


> I’ve avoided any testing because, as far as I know, there’s nothing preventative to be done. I’d love to hear otherwise.

Parkinson's is a nutritional disorder combined with genetic risk.

Zinc and Parkinson's https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125092/

Pyridoxine (B6) and Parkison's https://onlinelibrary.wiley.com/doi/abs/10.1002/ajmg.b.30198

Riboflavin and Parkinson's https://www.frontiersin.org/articles/10.3389/fneur.2017.0033...

Nutrition and Parkinson's https://link.springer.com/article/10.1007/BF02938409

https://www.frontiersin.org/articles/10.3389/fnagi.2014.0003...

https://www.sciencedirect.com/science/article/abs/pii/S00747...

https://link.springer.com/article/10.1186/s12883-014-0212-1


You could do a genetic test, Parkinsons has well associated genetic markers and consumer level companies can do testing of this (and others). 23 and me have a bit on it.

https://www.23andme.com/topics/health-predispositions/parkin...


Although if 23andme say you don't have the genes, you might still have them. Also they'll probably sell your data.


it's not a trivially heritable disease, genetic testing can't tell you with any real confidence if you'll develop symptoms

edit: you may be able to contact a parkinson's genetics counselor specialist which may be more useful


On a tangent, they also know the enzyme that causes SIDS and should have a testing program in place soon.


This sounds really interesting! Can you provide a link to more info?


"A 2022 study found that infants who died of SIDS exhibited significantly lower specific activity of butyrylcholinesterase, an enzyme involved in the brain's arousal pathway, shortly after birth. This can serve as a biomarker to identify infants with a potential autonomic cholinergic dysfunction and elevated risk for SIDS."

https://en.wikipedia.org/wiki/SIDS


Maybe this can stop the false prosecutions too. Or would they not be able to measure the enzymes in an autopsy?


May help, but it's still only one (potential) cause of SIDS.

SIDS encompasses a wide variety of risk factors. For example, heart pathologies are another common cause of SIDS. Additionally, stomach sleeping and inadvertent suffocation are other common risk factors.


The first study has 3 patients. The second study is a little better, but not by much. Both have the same first author. If this were legitimate, some academic medical center in the US would have picked it up. Parkinson’s is a huge target, and this kind of thing makes a career. This is likely on the same level as horse dewormer for COVID.


We detached this subthread from https://news.ycombinator.com/item?id=35770871 and marked it off topic. Please don't take HN thread on generic flamewar tangents. This is in the site guidelines:

"Eschew flamebait. Avoid generic tangents."

https://news.ycombinator.com/newsguidelines.html


> This is likely on the same level as horse dewormer for COVID.

That something sounds strange doesn't particularly lead me to question the likelihood of efficacy.

The evidence on something's efficacy leads me to question something's efficacy.


>This is likely on the same level as horse dewormer for COVID

You mean something that's demonstrated to have a statistically significant protective effect in a majority of studies but was attacked mercilessly by the pharma industry and the media they fund because they can't profit from a generic drug like that? https://c19ivm.org/meta.html


Looks great .. dive in (talk to your local professional epidemiologist) and it's a skewed collection of low N studies mixed in with studies in regions with large intestinal parasite issues.

Does horse dewormer do anything significant for large populations in first world countries?

No. (Save for regions with a intestinal parasite problem)

Elsewhere it gets rid of a significant number of parasites, making people healthier, and improving their chances WRT everything else, the common cold, influenza, COVID, etc.

If you have worms, take a dewormer course.

If you don't .. it won't do diddly squat for COVID.

Statistics!! (Sometimes there's correlation but that ain't always causal).


[flagged]


The fact that the only part of everything they said you have any response for is the term they used to describe the medication, and then used it to dismiss anything else - that doesn't make you seem especially free of irrational thinking yourself.


Red herring fallacy, as a response to tone policing or dictionary or whatnot.


not an argument and fallacy fallacy


Fair point, it's also effective against a wider range of parasites, head lice, eyelash mites, and skin conditions.

In the case of COVID in populations sans those conditions .. not so much.


In addition to head lice and eyelash mites, it might also be useful to point out it is the only drug to win a Nobel Prize for treatment of infectious diseases. Used by BILLIONS of people. May I remind you that you referred to this drug as a horse dewormer before you were called out.

https://pubmed.ncbi.nlm.nih.gov/34466270/


Appeal to authority & false equivalence (apples & oranges); just because it's won a nobel prize doesn't mean it's a miracle cure against the 'rona.

I'm already dubious of the article you linked because the title uses appeal to authority (nobel prize winning) and emotional language (new global scourge).

I won't disagree that ivermectin improves life expectancy in some of those studies, but it doesn't seem to be effective in environments with less parasites.

Note also that it focuses on fatalities, not getting the disease, curing it faster than its natural course, or preventing it.

For a great meta-meta research, see https://astralcodexten.substack.com/p/ivermectin-much-more-t...


I didn’t even say anything about covid. I was refuting that it should be referenced as horse dewormer. You seem to have some major bias as well.


FWiW no drug has ever won a Nobel prize - researchers are awarded such prizes.

Specifically William C. Campbell and Satoshi Ōmura shared the 2015 Nobel Prize in Physiology or Medicine for their work developing a new drug, Avermectin.

From the actual press release from the actual Nobel Prize Committee [1]:

    which was subsequently chemically modified to a more effective compound called Ivermectin.

    Ivermectin was later tested in humans with parasitic infections and effectively killed parasite larvae (microfilaria).

    Collectively, Ōmura and Campbell’s contributions led to the discovery of a new class of drugs with extraordinary efficacy against parasitic diseases. 

So, in actual fact NOT used for treatment of "infectious diseases" but for treatment specifically of parasitic diseases because it was developed to be a highly effective dewormer that kills roundworm parasites.

The Nobel Prize press release that you yourself cite (although apparently have never actually read) depicts Ivermectin as a Horse Dewormer (see figure 3) - it also deworms cattle, humans, pigs, etc.

As a highly effective dewormer it is obviously positively correlated with health improvements in any large population with significant parasites - killing parasite improves overall health, more food eaten available for the host, improved immune responses, etc.

Hence the reason for many global studies showing positive results following Ivermectin treatments.

Hence also the reason quacks in the US started pushing propaganda about supposed effectiveness against COVID, setting up smoke and mirror site such as the one linked above, and spreading sly not quite untruths such as the Nobel Prize one you've repeated.

Do please read the original 2015 press release in full.

[1] https://web.archive.org/web/20151005210425/http://www.nobelp...


Ivermectin is a protease inhibitor, among other possible mechanisms. They developed Paxlovid to work in a similar way, but it seems to be not effective whatsoever.

Then you have Remdisiv, which definitely killed 10's of thousands of people, if not more. That's the real story of COVID, at least in the US. The countless people that were experimented on with one of the most dangerous drugs to be invented in recent times.


Not to unnecessarily shit on the parade, but I’m not sure this is by itself all that exciting, and calling it a breakthrough seems like an exaggeration. Diagnosing Parkinson’s isn’t really an issue - worst case you give the putative sufferer Levadopa and see if they respond. If they do, they’ve got Parkinson’s.

Not sure how much this really changes the time horizon for an actual treatment. It’s progress, ostensibly, but I’d quibble with categorising it as a breakthrough.


> I’m not sure this is by itself all that exciting

This actually seems pretty significant.

1) It gets us closer to understanding the pathology:

>> It also suggests that alpha-synuclein aggregation in spinal fluid is not a life-long trait but rather acquired as part of a disease biology process that ultimately gives rise to symptoms.

2) It gives us a higher resolution of detection.

>> αSyn-SAA can distinguish Parkinson’s from control volunteers with a stunningly robust sensitivity of 88 percent and specificity of 96 percent.

3) It shows different disease subtypes or mechanisms:

>> These results suggest that not all cases of clinical Parkinson’s symptoms are associated with the accumulation of alpha-synuclein aggregates as detected by this assay, and that LRRK2 variant carriers, in particular, may not show this pathology.

4) It gets us earlier signal:

>> This finding suggests that synuclein pathology could be detectable by this assay earlier than dopamine dysfunction is seen with DAT imaging, extending the window in which it may be possible to intervene with preventive therapies.

This is a valuable tool that will shed light on the entire disease pathology and guide further research and investigation into treatments.


Biomarkers are extremely important in any disease. They make diagnosis very clear cut but that isn't the main reason they are necessary.

What a biomarker really does is focus research for treatments, you know precisely what it is you have to change and to what level and how to measure it. This makes it a easy to target drug development and to measure whether it works. Without a biomarker you never know if the drug being developed will help or not and most drug companies stay away from diseases without one.


The problem the OP pointed out is a valid one. Alpha-synuclein is a biomarker for many neurological diseases

https://pubmed.ncbi.nlm.nih.gov/24262191/

So you might say someone has a marker for Parkinson's and they might get another neurological disorder.

They tried these treatments in Alzheimer's and it failed. Why? because it is just another symptom and not the fundamental cause of the disease.

It is a good biomarker for poor health, but it is not a good biomarker for any specific disorder.


They are working towards not requiring spinal fluid for the test.

So it's possible that it could end up being a non-invasive test that could be done at regular intervals early in life.

Especially given that 15% of people with Parkinson's have a family history.


Finding subtypes before clear symptoms is obviously superior for testing earlier intervention and allowing patients to make a living will with fuller faculties.


I just found out about Thiamine (vitamin B1) megadose therapy for Parkinson's:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3762356/

Another study: https://pubmed.ncbi.nlm.nih.gov/26505466/

> Conclusions: Administration of parenteral high-dose thiamine was effective in reversing PD motor and nonmotor symptoms. The clinical improvement was stable over time in all the patients. From our clinical evidence, we hypothesize that a dysfunction of thiamine-dependent metabolic processes could cause selective neural damage in the centers typically affected by this disease and might be a fundamental molecular event provoking neurodegeneration. Thiamine could have both restorative and neuroprotective action in PD.

This experience report of halting Parkinson's: https://youtu.be/iuSOQOTyB9w


https://www.michaeljfox.org/news/thiamine-vitamin-b1-and-par...

The Michael J Fox foundation is more muted and says evidence is still missing. There have only been 2 trials and both were missing a placebo control group.


It's for the US and Canada only.


Imagine having Parkinsons and being in the placebo control group.


I used to share this sentiment for Parkinsons and other currently-intractable conditions. I still do sometimes, depending on the circumstances of the patient in question.

But the thing that stopped me generalising this was seeing second-hand that trialing a new treatment can be extraordinarily dangerous (and/or fatal).

Imagine being in the experiment group and the untested treatment being a catastrophic failure.


If a treatment in a placebo controlled study shows a vast improvement over placebo, the studies are sometimes finished early and are considered 'unethical to continue'.

e.g. HAART for HIV/AIDS.


Today we should assume that it's harmless to get the placebo.

Only if a trial shows extraordinary consistent benefit without drawbacks would they stop it because the placebo group is harmed for lack of access to the treatment.


You're thinking that even a gamble on untested / unverified treatment might improve their lives; it might, but it might also do nothing, make it work, or worst case kill them.

But I get it. My partner has an untreatable condition (like EDS, but without the genetic markers); they'd jump on any kind of hope, even experimental at this point.


Imagine symptoms improving being in the placebo group?

What are the statistics on that?


Being part of a rigorous process by which a cure may be found? Sign me up.


> 100 mg of thiamine administered intramuscularly twice a week

Is it possible to get anywhere near this much with dietary thiamine?


I read somewhere that gut can only let around 80mg thiamine/day and gut gets saturated over time, so only IM/IV would work long-term.


> Is it possible to get anywhere near this much with dietary thiamine?

High thiamine food stuffs have a few milligram at most so it would take some effort. However, many B1 vitamin tablets have 100mg-300mg, although I wonder how well that is absorbed compared with an intramuscular shot - it would seem that you could consume the equivalent of 200mg a week.


If this Was discovered 10 years ago, I’m assuming it must be fairly limited in helping, or the results haven’t lasted or something?


The cynic in me assumes that it's because this is not a patentable drug.

EDIT:

MJF foundation is aware of it at least - https://www.michaeljfox.org/news/thiamine-vitamin-b1-and-par..., but points out problems with the study. Further Googling quickly leads to the usual quackery about the magical properties of different supplements and vitamins. Hope this goes somewhere though.


This is such a horseshit characterisation of medical research.

Everyone bangs in about the medical industrial complex, and points to either herbs and vitamins, or more recently ivermectin, or hydroxychloroquine.

Everyone conveniently just rolls over the fact that steroids (also patent free) were rapidly identified by a massive research study in the UK, became standard of care, and saved hundreds of thousands of lives.

Is the pharma industry broken? Yes. Are there doctors who are conveniently leaving the cheap things on the shelf so a pharma company can profit off misery? Doctors are people too. In the most extreme form of this conspiracy thinking, apparently no doctors get or die from cancer. Just think on that for a second


No way. About five years ago there was a quack-y study about reducing death in sepsis which called for high-dose vitamin C, thiamine and steroids. None of these are patent protected. The first study purported to show a 100% reduction in mortality. There were many RCTs done after this which did not bear out the effect, and it has now essentially been proven to be ineffective. it is possible to fund studies without industry money.


Who actually thought that steroids help with an infection? Don't those usually make you more susceptible?


If most of the actual harm is being done by your immune system going into overdrive, then yeah, steroids can help. You'd want to simultaneously treat the infection, of course.

"Multiple randomized trials indicate that systemic corticosteroid therapy improves clinical outcomes and reduces mortality in hospitalized patients with COVID-19 who require supplemental oxygen, presumably by mitigating the COVID-19-induced systemic inflammatory response that can lead to lung injury and multisystem organ dysfunction."

https://www.covid19treatmentguidelines.nih.gov/therapies/imm...

But yes, you're also right that it usually makes you more susceptible to infection because your immune system isn't working as hard.


I can see that in some cases. I doubt that would be beneficial in the case of sepsis, right?


Actually, it's complicated, and there really isn't consensus one way or another.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5949415/

"Seventeen meta-analyses of these studies have been performed and have similarly shown conflicting results with some demonstrating a survival advantage (4-6) while other have not (7-10). Consequently, true equipoise exists with regards to the clinical benefit of corticosteroids in patients with severe sepsis and septic shock.

...

In summary, the use of corticosteroids in patients with severe sepsis and septic shock is not associated with improved patient centered outcomes, however this treatment is safe and without an increased risk of complications. Corticosteroids appear to have synergistic biological effects when combined with intravenous vitamin C and thiamine and may be associated with improved patient centered outcomes (21)."

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8604467/

"In this review article, we reviewed a total of eight different articles being done in last 10 years, relevant to the clinical outcome and effects of corticosteroids. Among those, two demonstrated improved clinical outcomes, two showed both improved clinical outcomes and decreased mortality, three showed increased adverse effects, and the remaining one showed unequivocal results."


Interesting


During COVID, steroids were rapidly identified as providing a positive survival benefit and became standard of care.

There is actually a good reason to think that steroids are beneficial in severe infections. This is because often in a severe infection/inflammation, a big portion of the damage is done by the inflammatory response.

Reading about the pathophysiology of influenza 13 years ago after H1N1, I came to this conclusion, and it was trialed, but good quality studies showed it to not be effective.

COVID has a slightly different pathophysiology and in COVID it works.

But yea, as a rule, it’s not a good idea to dose with steroids if sick


I've taken steroids when I had a virus because the symptoms caused by the virus were severe. The doctor made it clear that I should take it as little as possible, but it was "your throat is going to close up OR it takes a little longer to get better".


Chronically, yes. Sometimes they can help address a more serious acute issue.


There is a fair amount of research on diet and nutrition. Much of that is not patentable. For example, I think a recent one was all over the news about magnesium rich foods lowering risk for dementia. Unfortunately this area sees a lot of back and forth in some areas (like with eggs).


Most doctors would laugh at vitamin supplementation even at pharmaceutic megadoses despite people reporting they feel much better. I have seen both GPs and a neurosurgeon laughing about it.


When in doubt, just throw the kitchen sink at the problem.

https://www.hangoverkw.com/


Is it because of thiamine dysfunction or because thiamine at 2000x RDA doses acts as a carbonic anhydrase inhibitor, i.e. would acetazolamide work the same?


This further assures my thought that Parkinsons is caused by gut bacteria


Say more about your theory


A gut bacterial amyloid promotes α-synuclein aggregation and motor impairment in mice

https://elifesciences.org/articles/53111

Note, this was in mono-colonized gnotobiotic mice.


Published in the "Journal of Integrative and Complementary Medicine", "The leading peer-reviewed journal providing scientific research for the evaluation and integration of complementary medicine into mainstream medical practice."

"Integrative and Complementary Medicine" is a fancy way of saying quackery.

Also, the video you linked to is on a channel run by a person describing himself as "a certified functional medicine practitioner & naturopathic nutritional therapist [..]. He enjoys making videos on a wide variety of health-related topics ranging from nutritional biochemistry to circadian biology, animal-based nutrition, and the dangers of electromagnetic radiation."

No further questions, your honor.


You know what you're right. But not far behind these quacks are neurologists.

If you've ever had someone in your family that might have had Alzheimers or Parkinsons you'll know what I mean.


I think that is being unfair. It's the sad reality that for many neurological conditions we don't have good treatments or cures. However, things like levodopa are godsends for many with Parkinsons, for example.


My pet peeve is people dismissing potentially very valuable scientific results because they’re afraid of quackery…

Yes we should be cautious but no we should not dismiss. In fact I consider myself very fortunate for stumbling on this information as it may be very helpful for someone I love and I want to explore every possible way that can help.


That's the precise essence of why quackery is dangerous. People are searching for "every possible way that can help" and quackery can easily exploit that natural tendency. (I am not qualified to render any opinion on whether this specific protocol is quackery.)


The problem is the lack of incentives to take the “huh that’s interesting, but I don’t know if I can trust it because it’s published in a quack journal” … and ever reproduce the research and get it into more trusted more prestigious journals.

There’s a reproducibility crisis in many fields of research, and medical research has multiple confounding factors, the “no prestige in just redoing the research”, lack of money for trying things that might fail to generate RoI for pharmaceutical companies, and the general medical research problems of clinical trails and ethics review and all the other stuff involved in good quality medical research.

Consequently this stuff gets thrown in the quackery bucket and ignored. It’s frustrating to see things that won’t hurt anyone to try again and properly debunk or expand the evidence for, winding up in an ideological trench war where the outcome is getting to enter round two of the “funding your actual research” trench war.


If you had a legitimate research finding, why would you publish it in a quack journal?

Presumably, because the more prestigious journals declined to publish it.

Why did all of them decline to publish it? There was probably a reason. A paper being published in a quack journal does actually carry a signal about the quality of paper, IMO. No one turns down publishing in Cell or Neuron to publish in Donald's Journal o' Quackery and Crockpot Recipes.


Yes, the point you’re making is valid and I generally speaking agree with it. The issue isn’t necessarily that it was published in a quack journal, it’s that now this idea has been published in a quack journal it’s “tainted” and suggesting that it be looked at again for any other reason than some significant new evidence discovered completely by accident (because you’re a quack too if you believed the idea in this paper) and it has to be pretty significant evidence too (otherwise it might look like you are cherry picking evidence for your quack belief) and only then can you consider the idea worth properly studying… all because by originally being published in a quack journal, the idea has the taint of quackery.

Now most quack research is not particularly useful… but it can be made more useful to society if it’s used properly, we should be more willing to publish reproductions and failures to reproduce existing research, and we should be encouraging early career scientists in all disciplines to take this kind of quack research and to prove it wrong, it’s all there to disprove, easy done. We would get more critical thinking in our research students we would get more evidence to disprove other quack research and every now and then we might even stumble onto something good that would have gone ignored as just quackery for an unknown period of time.

If we want to fix the reproduction crisis we can’t ignore the shit research papers and only reproduce the good ones we think might work, we need to be willing to look at research like this, which involves a pretty/relatively harmless high dose vitamin regimen that can be easily monitored by a clinician performing the research work (double blinds of course) and then we go from “idea that won’t be touched again and quacks try to convince people with flimsy research” to “idea conclusively proven or disproven and scientifically have settled the question without leaving reasonable doubts that can be used by quackery peddlers or others mis-using the scientific method for their own gain.


That's also the precise essence of throwing out the baby with the bathwater.

I'd much rather have the information in front of me so I can evaluate it and make my own determinations. If the parent commenter had their way I would've never seen this information. Now I can actually vet it out and do my own research.

I think it's infinitely more dangerous to deprive people of information.


> much rather have the information in front of me so I can evaluate it and make my own determinations

This is the danger. Most people, myself included, are not qualified to make that determination alone. In this case, as expected, it looks like it was crap [1][2].

I'm not arguing in any way for censoring anything. But there is legitimate danger when people, often desperate, compare legitimate medical research, which will be subdued, with quackery, which will be ostentatious, and then, worst case, reject the actual medicine or hurt themselves trying to administer rogue therapies.

[1] https://news.ycombinator.com/item?id=35771376

[2] https://news.ycombinator.com/item?id=35771048


One notable exception to that is Kyrie Irving and other Covid vaccine skeptics, who were amazingly somehow able to "do their own research"


Counterpoint. Historically people have not been able to evaluate these types of claims. See the history of snake oil salesmen and the origins of the Food Drug and Cosmetics Act.

I don’t think it is a problem when people look at stuff, think it is interesting and try something relatively benign on themselves. For me the problem is when people start trying to play doctor without medical training or license.


I agree with you in regards to the dangers of snake oil and snake oil salesmen and the general inability for the vast majority of people to properly vet medical information.

That being said, I would say it’s unfortunately by necessity that people start trying to play doctor. I live in Canada, our healthcare system is currently in shambles such that it’s impossible to get timely care. Even the care we do get is time-limited and only focused on saving your life (which is great, but ignores the value of improving quality of life too). Also most of our medical interventions are so far behind the state of the art due to a Byzantine regulatory process that anyone actually trying to help a loved one with a health issue is forced to take matters into their own hands otherwise we fall through the cracks. The medical system is simply failing way too many people in Canada that it’s inevitable people Will take their health and the health of their loved ones into their own hands by necessity.


It's not fear, it's challenging a conclusion made by people based on their credentials. If the science stands up to scrutiny and peer review, then great, but if it doesn't then it's not true.

The quackery label comes in not from the science but from the people behind it and the monikers / titles that they applied to themselves - unrecognized and not formally tested monikers / titles.

The formal testing is so that there's a proven and traceable minimum knowledge and background behind a person's statements. Like a bachelor's degree for a software engineer vs a two week boot camp.


Reminds me of this post I saw on CompSci Reddit once. A person claimed to have made an O(n) algorithm for finding loops in a graph (or something like that), and he posted the source code. The comments were all in the line "big if true, but I'm going to have to see a peer reviewed paper" to which he answered along the lines of: "I'm paid to write code, I'm not paid to write papers. I made this algorithm solve a problem at work, take it or leave it".

The thread died without anyone actually checking if his algorithm worked or not.

Who knows...


Do explore it, but check other (reputable) sources for the effect on Parkinson and for counter-indications (although there don't seem to be obvious ones).

The journal, however, is bad. Looking for articles, the first I found claims that sounds of nature have a positive effect on gambling addicts, something unwarranted by the actual experimental conditions. The peer review and editorial process seem to be lacking.


I mean sounds of nature have a positive effect on most people so that sounds like low hanging fruit, lol.


You did not, in fact, stumble upon information. You stumbled on a person making statements. There’s a difference, especially when lives are at stake.


In this context they're functionally equivalent, in that anyone making statements is also communicating information. Could you explain the difference that I did not grasp?


Agreed; this is akin to the "woo" applied writ large to the lucid dreaming phenomenology; or anything "metaphysical" crossing into "empirical" -- I have a fondness for the UAP topic and it's poster child for this effect. I know there's a grain of truth in the bucket but the wackery is beyond my ability to dredge.


This isn't an unfounded fear of quackery, they've supported their view to an extent.


God bless you for sharing this. Thank you.


Take a look at zinc instead. It helps increase the activity of enzymes that break down alpha-synuclein.

https://academic.oup.com/hmg/article/23/11/2791/621896




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