Mitochondrial DNA damage triggers spread of Parkinson’s disease-like pathology | Hacker News Reader

Mitochondrial DNA damage triggers spread of Parkinson’s disease-like pathology

eurekalert.org

181 pointsgeox32 comments

> “Furthermore, we are dedicated to exploring potential therapeutic strategies aimed at restoring normal mitochondrial function to rectify the mitochondrial dysfunctions implicated in the disease.”

I can't help but feel excited. Breakthroughs in Parkinson's, breakthroughs in ME/CFS, breakthroughs in long covid. And the cool part? They all seem to follow similar hypotheses of mitochondrial dysfunction.

https://www.science.org/doi/10.1126/scitranslmed.abq1533

https://www.washingtonpost.com/health/2023/09/17/fatigue-cfs...

Watching from a distance, I think a lot of our fast progress recently is because of better tooling. Better ways to see what is happening at a microlevel, and manipulate it too.

Like someone could run endless experiments on how to "balance the four humors" perfectly and get nowhere with all these diseases, perhaps not even be able to clearly define and distinguish them from one another.

Absolutely. It is an exciting time for science. And also for someone who may have one of these unexplainable diseases.

Can we possibly expect something similar for other neurodegenerative diseases such as Alzheimer's?

We have investigations into mitochondrial genetics and Alzheimer's. There's still a lot to learn but it's probably safe to assume there's a lot more going on. Treatment and even prevention for most will likely rely on attending to more than just mitochondrial abberations.

Physionic: Fasting and Overeating - How you Change your Mitochondria. [Study 32] https://www.youtube.com/watch?v=KQBmtzT4VTU Goes into great detail in how abundance of energy causes Mitochondrial to split into smaller pieces and go into high churn (low ATP output) but when in a low energy environment the Mitochondria join into longer chains and actually change how they work. There is other talks in how long chain Mitochondria outputs being used in brain cell inter communication and having said Mitochondria being too small massively inhibits those systems.

Mitochondria are at the center of a lot of key processes in general. They play an important role in regulating cell death and free radicals in the body. They also play a role that is still being studied in what membrane receptors are transported to the surface in neurons.

There's a lot that intersects at the mitochondria making it common across many pathogenesis and a very delicate system to interfere with (not ideal for intervention)

Crazy how important mitochondria are when you consider the evolutionary history.

Just so, so, so unlikely to happen to my small mind and stunning how far multicellular life has come with this symbiosis.

It's an exciting time and I think we are in a lag where all the tremendous progress in microbiology and related tech is starting to kick into high gear in delivering results. Basic things like being able to sequence whole human genomes for $500 and super cheap ability to introduce perturbations and observe their effects (CRISPR) have propelled research tremendously over the last few years, but many studies involving humans just take years to complete regardless of tech, so we are just starting to really see the results of these come through. I expect the next decade is going to see unprecedented progress in understanding of all kinds of severe diseases, as well as (with some further lag) development of therapies.

First clinical trial of CRISPR base editing started in Sept this year after only being known in 2016. Exciting!

yeah how do you solve this problem though?

once enough mtdna has been depleted it's irreversible

Unfortunately maybe the solution is not a cure but a vaccine that prevents depletion.

The actual paper title is "Mitochondrial DNA damage triggers spread of Parkinson’s disease-like pathology": https://www.nature.com/articles/s41380-023-02251-4. Parkinson's is a notoriously complex disease with multiple etiologies and subtypes. While this is particularly exciting to see (I have a loved one with PD), the EurekAlert article really misses the critical "PD-like" modifier.

Thanks - let's use that title above.

Fluoroquinolone antibiotics (like cipro, levaquin) wreak havoc on your mitochondria, including on mtDNA [1]. I doubt there's a link between FQs and Parkinsons. At least it would be easy to falsify that hypothesis. But FQs can cause permanent damage in humans, and it's interesting to see that mtDNA damage (which FQs cause) can have effects like the linked article show.

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6182158/ [2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6648947/

This happened to me. I had a drastic reduction in VO2 max since taking them that has remained permanently.

Happened to me too- my joints are still messed up. Really wish doctors did a better job informing you before putting you on some random antibiotic that can cause so much damage in the body.

it's 9 years later if I jog for like 1 minute (which I can't really even do) I still have severe pain in my ankles and electric shock sensations in my feet. It never went away. Permanent damage.

I used to be able to just run forever and never have any pain. Just 1 week prior to Ciprofloxacin.

It's sad to hear these stories. There seem to be so many of them online, which you can find if you search for "floxies".

I wonder when medicine will catch up and recognise the danger of fluoroquinolones. I've heard that in the US they have a "black box warning" on them. In the UK where I live the only warning you get is from your GP that you might experience tendonitis, and if that happens to stop taking the medication. No warning of life altering and crippling illness.

I was given two courses of Ofloxacin back-to-back in 2019. After four years of being the most ill I hope I will ever be, I am now finally starting to feel normal again. My symptoms were chronic fatigue, chronic gastritis, inflamed liver, liver cirrhosis, crippling anxiety (including derealisation), and inability to eat most things without horrendous bloating and brain fog.

No doctor I spoke with would correlate my illnesses with Ofloxacin, and all considered the fact that my symptoms began with my prescription as nothing more than coincidence.

My advice is never, ever take a fluoroquinolone antibiotic unless absolutely necessary. I certainly will never touch them again unless I am in mortal danger and all other options have been exhausted. They should not be handed out so carelessly.

Another 'floxie' here.

While mine was 'mild' it was still scary as I was prescribed Cipro along with an NSAID which is contradicted in the Cipro literature.

My issues were the joint and tendon pain to an extent, but mostly neuropathy related like tingling, feeling 'static' all over, twitching muscles/spasms, etc. I also had the anxiety, derealization and digestive issues.

Eventually I started feeling better (reading recovery stories online helped) and today only have minor issues such as occasional joint pain, inability to tolerate NSAIDs, on/off digestive issues, and rarely the nerve issues. I can walk long distances, but do find exercising to be a struggle still.

Like you, I tried with a doctor once and just gave up. I have a little warning note in my wallet not to administer any FQs outside of life saving requirements.

It's sad that to this date, they are still handed out like candy for the slightest suspected infection when there are plenty of better tolerated and less dangerous alternatives.

if you can't exercise really that's not mild

Well, crap. My mom complained about tendon damage issues after taking Cipro. I don't remember which tendons, probably legs, but I don't think she ever felt recovered from that. She probably only got generic warning statements that some people may experience side effects.

Anyway, antibiotics causing damage like this sounds like it could have triggered an auto-immune problem. If so, then that is a large quagmire.

There is at least a case study where fluoroquinolone administration improved the symptoms of a patient with Parkinson's disease.

https://pubmed.ncbi.nlm.nih.gov/27532488/

This is both interesting and scary, that FQ's CNS/GABA disrupting effects could somehow interfere with the pathology of Parkinson's. Doesn't seem worth it for the potentially permanent side effects from FQs.

This study seems to amount to “mitochondrial DNA damage is caused by mitochondrial DNA damage”. Yes, it’s interesting that it can spread once initiated, but what is causing the initial damage that’s setting off the chain reaction? The only clue seems to be in this sentence:

>By examining both human and mouse brains, researchers discovered that the damage to mitochondria in brain cells occurs and spreads when these cells have defects in anti-viral response genes.

So this is in response to a virus? That has been a theory for a very long time.

It also can be: toxins, hypoxia, immunity, and genetics. Any of these factors can initiate a mitochondrial dysfunction.

The paper discusses TLR4 and TLR9.

TLR4 is known to interact with nickel and cause mitochondrial dysfunctions.

If there's a virus involved it may be the virus is triggering the spread of the damage already done by nickel?

Nickel is a surprisingly good fit for my father...

Wasn't there another study earlier this year saying they found the cause of Parkinsons which is strains of some bacteria

Parkinson’s like a lot of neurodegenerative diseases has a complex set of triggers, causes, symptoms, prognosis and is unlikely to have one single cause as it’s not one single disease.

The gut brain link is a serious concern

I was told by a doctor that everything causes mtdna damage and it's sort of useless to define things in terms of that. Like saying because you have a skin condition like rashes that there is damage to the skin cells. Like yeah, of course there is.

The difference lies in the direction of the damage. If it comes from a cell to mitochondria then it is a normal situation we all (including your doctor) are used to. But if the damage comes from inside the mitochondria to a cell, leading to its dysfunction and eventually death, then we are talking about a so called mitochondrial dysfunction.

There is a big difference between these two conditions. The first one is natural and healthy, while the second one is pathological.

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