When will we have a biomarker?

Husband of

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For cfs, based on its current definition, never. And, unfortunately, that's what test for potential biomarkers are being measured against. As far as I Can tell noone has yet attempted to find biomarkers that fit a subset of those with cfs or to better articulate symptoms so as to better find the symptoms associated with each disease currently causing cfs.

Look at brain fog; as currently defined it could be caused by being anxious, depressed, hungover, drunk, over caffeinated, tired, overtired, stoned, having encephalitis, etc. yet all of these feel different so better articulation and consideration of other concurrent symptoms would go a long way to better understanding what the issue really is.

Simon wesselly in the 80s argued that cfs and depression were the same because based on the broad articulations of the symptoms he was right; as right as someone would be to say cancer and hiv and depression were the same if they were described as broadly as 'don't feel good'. This guy is now in control at the nhs despite either being incredibly stupid or incredibly evil.
 

Vladimir

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We are getting closer. Here is the summary (by GPT-4) of the recent study about blood biomarkers for anxiety. I think this is the road that will lead to the CFS/ME markers as well.

https://www.nature.com/articles/s41380-023-01998-0.pdf

This paper, titled "Towards precision medicine for anxiety disorders: objective assessment, risk prediction, pharmacogenomics, and repurposed drugs", discusses the increasing prevalence of anxiety disorders and the need for more precise and personalized approaches to their diagnosis and treatment. The authors propose a four-step approach to discover blood biomarkers for anxiety.

1. They used a longitudinal within-subject design in individuals with psychiatric disorders to discover blood gene expression changes between self-reported low anxiety and high anxiety states.
2. They prioritized the list of candidate biomarkers with a Convergent Functional Genomics approach using other evidence in the field.
3. They validated their top biomarkers from discovery and prioritization in an independent cohort of psychiatric subjects with clinically severe anxiety.
4. They tested these candidate biomarkers for clinical utility, i.e., the ability to predict anxiety severity state, and future clinical worsening (hospitalizations with anxiety as a contributory cause), in another independent cohort of psychiatric subjects.

The biomarkers with the best overall evidence were GAD1, NTRK3, ADRA2A, FZD10, GRK4, and SLC6A4. They also identified which of their biomarkers are targets of existing drugs (such as valproate, omega-3 fatty acids, fluoxetine, lithium, sertraline, benzodiazepines, and ketamine), and thus can be used to match patients to medications and measure response to treatment. They also used their biomarker gene expression signature to identify drugs that could be repurposed for treating anxiety, such as estradiol, pirenperone, loperamide, and disopyramide (Pages 1-3).

This research is significant because it addresses the urgent need for more precise and personalized approaches to the diagnosis and treatment of anxiety disorders, given the detrimental impact of untreated anxiety, the current lack of objective measures to guide treatment, and the addiction potential of existing benzodiazepines-based anxiety medications.
 

Osaca

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The only thing that seems is definite is that it won't happen within the next 3 years. Whether there'll be one within the next 5, 10 or 20 years, I don't know. If they solve Long-Covid, I'm fairly confident they'll make massive in roads in ME/CFS as well. If they don't solve Long-Covid, hoping that they would be able to untangle ME/CFS seems delusional.

I agree with what @Husband of of says, unless studies become more specific it'll be hard to find anything. I'd much rather see a new study saying 50% of people with ME/CFS have this and this and there are tangible difference amongst these people, rather than we used some ML classifier and obtained a 100% accuracy within our study and we don't know why and no other data will ever be touched.
 
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Wishful

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We'll have one when we have one. I expect they've ruled out all the obvious potential biomarkers, so a biomarker for ME will be something unexpected, and there's no way to predict when the unexpected will happen. You can't base predictions on history either, since a biomarker for some disease being found in a week, or one taking 37 years to find, means nothing for today's search for a marker for ME. Throw in new technologies, and it's even more unlikely to make a rational prediction. We might have a super-AI in a few years that can solve pretty much all medical mysteries, and develop better treatments for known diseases. Alternatively, we might suffer a global depression or world war or plague or super-storms that set back the pace of R&D.

So, we'll have one when we have one.
 

hapl808

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This guy is now in control at the nhs despite either being incredibly stupid or incredibly evil.

That's unfair saying stupid or evil - it might be both.

I agree with what @Husband of of says, unless studies become more specific it'll be hard to find anything. I'd much rather see a new study saying 50% of people with ME/CFS have this and this and there are tangible difference amongst these people, rather than we used some ML classifier and obtained a 100% accuracy within our study and we don't know why and no other data will ever be touched.

I actually think ML is being grossly underused to find biomarkers, as there are some algorithms that can make predictions AND can point out what metrics are being more heavily weighted.

If we ran ML on people who reported fibro, ME/CFS, Long Covid, healthy, MS, MD, HIV, cancer, and various other disorders, we might be about to find some similarities and point researchers in the right direction. We already have the technology.

But modern medicine is mostly about gatekeeping and dogma. Finally we're getting some acceptance of ML in specific cancer radiology, although my impression is the field has been better than current average human radiology for a number of years and the reason it hasn't been implemented is gatekeeping on datasets and dire warnings from those whose jobs are about to be replaced.

Medicine moves slowly, and it is an organism. Its main goal is to protect itself, not to help others.
 

Rufous McKinney

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This guy is now in control at the nhs despite either being incredibly stupid or incredibly evil.
but that is just one country. there are 100s of other countries. Where the Simon Wessleys' should not be running the show. Yes, I understand there is MORE than one of THEM.

That they do not include citations from Harvard or Stanford or Utah or North Carolina. Or Japan. Or Israel. Italy.
I expect they've ruled out all the obvious potential biomarkers,
I doubt it. Nobody is following up on the Subsequent Work necessary for anything to become a bio marker.

There seems to be virtually no incentive for anyone to pursue pinning that down.

And what good would a biomarker do us? When treatment is close to zero, or mostly n=1.


For cfs, based on its current definition, never. And, unfortunately, that's what test for potential biomarkers are being measured against.
if thats the case, there will be no forward progress.

How many ME research studies say: for a SUBSET of patients, X or Y is going on....(many many say this)

So if subsets are ignored and lame vague criteria relied upon, and then responses are viewed by asking people with serious cognitive problems to subjectively rate some exertion or another. Thats a pathway to failure.
 

hapl808

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And what good would a biomarker do us? When treatment is close to zero, or mostly n=1.

The biomarker is incredibly useful for developing treatments. It's much harder to study something when you have no idea who even has it. It would be easy to mix up MS and ME/CFS and LC and fibro and so forth.

So any biomarkers would be helpful, particularly ones that respond to treatment because surveys of, "Do you feel better?" are incredibly susceptible to confounders.
 

Treeman

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The theory that the condition is caused by immune dysregulation and persistent infections opens up questions.

What causes the immune dysregulation? So far they have discovered about 120 auto antibodies, but I've read there could be many more, maybe up to 3000. Similarly cytokinins discovered is believed to only account for a percentage of what there could be. If either of these, or both is causing or contributing to ME/CFS not until they are all discovered could a bio marker be identified.

I guess one positive is that research outside ME/ CFS could unlock the answer.
 

Rufous McKinney

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The biomarker is incredibly useful for developing treatments.
yeah, I realize thats likely the case....
particularly ones that respond to treatment
I'd vote for more of that....

"Do you feel better?"
agree..so fed up with this part. FIND SOMETHING MEASURABLE and replica table.

I just got alot more tests done....and yet those results sort of don't matter.

It would be easy to mix up MS and ME/CFS and LC and fibro and so forth.

its this necessary part, that seems to almost NEVER happen. Every paper announcing Potential Biomarker, is never comparing a diverse set of people with these types of illnesses. Nor are they focusing on subsets of ME, either (perhaps long covid will someday be a subset). Seems like I'll be long gone before anything like that ever happens. Maybe folks in their thirties now, might see it.

My daughter lived with a person with MS. I'd visit. She was really busy. I was barely operating. She gets to have an official illness, medical research, and is treated like it matters.
 

Husband of

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How many ME research studies say: for a SUBSET of patients, X or Y is going on....(many many say this)
I hope you are right but I don't really see this for biomarker studies. What I see is some studies that hypothesise about causes may suggest there are different subsets.

For biomarker or treatment studies the best I see is a throwaway comment at the end that suggests further research should be done to consider whether the biomarker or treatment might be applicable to certain subsets.

Ok throwaway might be a bit harsh given the researchers have just done what they could do with limited funding or time, but still it would have been great if they could have tried to look at subsets as part of their study.

But I hope you have seen differently. And, please, let me know next time you come across a study that actually investigates subsets in some way rather than merely suggesting there may be subsets and that future research should investigate based on Subsets.

Also, apologies for the negativity. Hope you are doing ok.
 

Wishful

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There's another problem: researchers might find a biomarker, but it will only be a marker for a downstream condition that a subset of PWME have. Sadly, it will probably be assumed to be definitive of all forms of ME, so some PWME will test falsely negative, and some people will test falsely positive and mess up studies. It's just not as simple as "finding a biomarker = problem solved",
 

Osaca

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It's just not as simple as "finding a biomarker = problem solved",
Yes. I feel like a vascular marker might be possible within the near future. Some inflammatory vascular markers as well as markers of endothelial dysfunction have received quite a lot of attention, especially in Long-Covid. This probably won't be unique to the disease, might not be applicable to everyone and might not be the root cause, but a biomarker isn't a solution for other diseases either, it's just often just a necessary first step that, not only shows some physiological properties of the disease that can be aimed to be untangled, but casts a large shadow on its psychologization.
 

Andryr

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I may be too naive hoping the NIH ME/CFS intramural study results will reveal something. Avi Nath said they found something important and biomarkers will be the next step. The study is in review, hope it won't take years to publish it.
 

Judee

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