What if they find a biomarker?

I have a feeling that OMF might be closing in on a biomarker. But if there is a biomarker and it reflects something downstream, is it possible that the biomarker might not be useful in identifying treatments? Are there examples of other diseases where a biomarker was found, but it was not useful in identifying treatments?

Maybe the biomarker will be useful for disability/insurance purposes but not for identifying treatments?

 

Until we better understand the aetiology of ME we have no clear idea what treatments might or might not be possible. There are a range of options:
- that ME is totally reversible by some form of treatment or procedure, such as a cancer that can ‘cured’ by surgically removing the tumour
- that ME involves irreversible damage but can be compensated for by a treatment, such as thyroxine given for hypothyroidism
- that ME involves irreversible damage for which there is no current treatment, such as the long term loss of brain cells following a CVA

For me the most hopefully sign of the possibility of a treatment is the variability in ME systems, suggesting if an individual experiences good days, the underlying deficit may not be irreversible. However I also have the suspicion that the longer an individual has the condition and the more severe the condition is, the more likely irreversible biological changes have occurred.

I suppose there is a question whether a reliable practical clinical assessment or test for ME requires an understanding of the aetiology of the condition or not, though I suspect if we do establish an accurate biomarker it would at least point us to where we should be looking for treatments. However it is at least theoretically possible that we have a consistent biomarker, that gives no conclusive answers to nature of the disease process.

Interestingly what worries me about any possible biomarker is that, if what we group under ME/CFS is a heterogenous group of conditions and not everyone currently fitting in the diagnostic grouping will display this marker. Consequently that though for those testing positive a biomarker can only be a good thing, there may be a subgroup that test negative and are left out in the cold.

I wonder if as we refine our definitions of ME, for example with the introduction of the idea that PEM is a necessary core symptom, what happens to the people left behind. What has happened to all those people that fitted the Oxford criteria for CFS, but don’t display PEM so no longer are regarded as having ME/CFS? Are they achieving more accurate diagnoses and better treatment or is there a group of people with idiopathic chronic fatigue that are even more prey to the MUS and FND vultures?

[added - Sorry this is a bit of a free association on the theme of the thread, rather than a direct answer to @Jaybee00 ’s question. There are a fair number of conditions where there are useful clinical diagnostic tests but we have no, or only very limited, treatment options, for example MS or MND (ALS). ]

 

What facts underlie this feeling? Do you have some inside information?

 

Yes, I agree, having PEM as an exclusionary symptom can lead to a lot of false negatives. Me for example, I never had PEM for the first 13 years of my illness. I think some people just have a very high PEM threshold, meaning that they really need to push themselves in order to induce it. Other people may have their energy and stamina levels so reduced that they simply cannot push themselves hard enough in order to induce PEM.

That was the case with me. Namely, I had a high PEM threshold, but also very reduced stamina - I could only run about 1 to 3 minutes before being out of breath and unable to anymore (this was 100% the result of CFS, since I was very athletic despite being ill). So the result was, I never got PEM, because: 1. I had a high PEM threshold and 2. I was too tired to push myself hard enough in order to trigger it.

Furthermore, many people may get PEM, but simply not realize it is PEM. Another example with me - looking back, during that 13 year period, I did experience some weird symptoms the day after very intense activity on a few occasions, however at the time I would have never thought this is due to CFS, I attributed it to sleeping badly or what I ate the day before.

I also believe that having this symptom as a requirement hurt me personally. Namely for 13+ years I wasn't sure I had CFS, because I simply did not have the main (required) symptom. Then back in 2017, I pushed myself really hard (probably the hardest ever), had the worst crash ever that left me with permanent symptoms and sent me from mild CFS to moderate over the following months. I think people should be made aware that you can still have CFS even without (noticeable) PEM and that they should be very careful when exerting themselves. In words, just because you don't have PEM, doesn't mean you can't trigger it, so be careful!

 

This really worries me.

Also, a biomarker may not be widely accessible, e.g. if it requires expensive scans or the sort of tests only a few labs in rich countries can do.

On the positive side, even such an impractical biomarker could still lead to a better understanding of the pathophysiology of ME. It may not directly lead to treatments but it could well be a piece in the puzzle.

 

I'm kind of like you. I do have PEM but my threshold is very high, so I have to do something really demanding to trigger it. However, I am almost always in a state of worsened symptoms due to extreme weather sensitivity, to the point that I cannot really work or plan because I never know when another weather change happens. I can avoid PEM, I can do nothing about this. Yet, I had a sudden, EBV-triggered post-viral fatigue that turned into ME/CFS, I have about 15 symptoms and I'm exceptionally healthy on paper, so I'm not sure what else this could be. Yet, I'm terrified a test would tell me I don't have ME/CFS and then what would save me from doctors telling me it really is just all in my head?

 

What if a biomarker is found? Well the study needs to be peer-reviewed and published, and then the work needs to be validated and replicated.

 

Hi there, I see you are new to the forum, welcome.

You raise some good points about the test. I do think there are sub-groups to CFS, ie. not everyone suffers from the same thing, so your fears are not unfounded. Maybe this new biomarker / test will only detect a sub-group of patients, which will obviously suck for the rest.

Funny you mentioned you have 15 symptoms. I probably have even more, they are too many to count actually. What's interesting is that I have had many transient symptoms, ie. symptoms that last for a while and then go away. I probably have around 15-20 permanent symptoms like you, but if I include the transient ones the list would be much longer. I've had dizziness, head / ear pressure, bladder hyperactivity, nausea, loss of apepite, etc, etc. some of those come back from time to time, others I've had for weeks or months and then they went away.

They are so many that I don't even talk about all of them IRL or else people will think I am crazy. CFS is really a very peculiar and puzzling disease.

As far the weather sensitivity goes, that's very interesting, I don't have it, but it's not surprising at all as I've read so many accounts of people being sensitive to random things (foods, cleaning products, noises, mold, etc.). Myself, most of my sensitivies are to foods (that I can avoid) thankfully.

 

I have actually found some other people too with the weather sensitivity thing (in other groups), so it may not be very common but some people seem to be affected. I always think it might be similar to someone with migraine and their weather triggers. Except my headaches are sinus headaches without mucus, but my worst symptoms are the extreme level of fatigue and the brain fog during these times. But there are others too.

Thank you for the welcome. I think I should go and introduce myself properly in the apropriate thread and detail my issues there.

 

I have distinctive delayed PEM. If I go over my energy limit I will always get delayed PEM. It doesn't matter how well I feel on any particular day. I highly doubt that the OMF has figured this.

Years ago when I didn't have autonomic issues I was a lot more functional. I could go out for short outings and not worry or feel anxiety because I needed to lie down to 'recover'. I would like to see a specialist to test and treat my autonomic issues. That alone would allow me to be more functional in my daily life. The autonomic issues (positional intolerance) are very disabling and make PEM feel worse.

 

I didn't develop PEM for several years after onset because I had PVFS and rested for 6 years. When I recovered from PVFS and felt 80-90% improvement, I developed PEM only after I started exercising again. Over the years PEM intensified the more I exercised until I finally realized that this wasn't going away.

The pathophysiology of PEM is always there with ME, this is the distinctive difference between PVFS and ME.

Unfortunately, I see the term PEM being used everywhere for all sorts of ailments on the net.

 

The whole concept of biomarkers is very confused. Recently (2018) there was an investigation that found various agencies use different definitions of biomarkers. See for example https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5813875/

Often when biomarker is cited, especially by doctors, it means diagnostic biomarker. There are a lot of other kinds.

At its simplest level, not often used this way, a biomarker is simply a measurable biological anomaly. ME has more than 2500 of those, and I stopped counting years ago. This is how I think of biomarkers myself, and will use "diagnostic biomarker" or some other designation to mean one of the alternative definitions. To me a biomarker is just a biologically significant marker.

Diagnostic biomarkers either need to be unique, or there must be an easy way to differentiate between disease states that share a biomarker. ME shares biomarkers with at least sepsis, severe burns, and African Sleeping Sickness. While it is probably not hard to rapidly differentiate between these four, it does raise the question as to how reliable these markers might be because they might exist in many other diseases and this has just not been discovered yet. If a biomarker is found in many diseases it is much less useful diagnostically.

Take the nanoneedle. It is highly likely in my view that it will find abnormalities in a range of diseases, including mitochondrial disorders. However it might be used in other ways than diagnostically.

Outcome biomarkers are very useful. The nanoneedle might be used as such. If a treatment improves results measured by the nanoneedle it might indicate the treatment helps . . . but there are potential confounds that might invalidate that. Its an indicator, not proof. It might tell us what is interesting so we can do further studies.

We know so very much about what is going wrong in ME right now, but we don't have a proven core causative mechanism. I suspect the comment on a biomarker was on such a postulated finding. Many groups may have found one, including OMF, or they might not have. In either case there is a long process to go through to test such a marker. There is no substitute for doing the science, which takes time and resources. All our groups lack sufficient resources.

In ME we might be able to find biomarkers that show severity or outcome, or even subgroups. There are many possibilities.

The mere knowledge of a biomarker does not, in my view, necessarily lead to accurate diagnosis or effective treatment or cure. Its a step along the way.

If ME is more than one disease, or some kind of spectrum disorder, we might wind up with many more than one diagnostic biomarkers.

The key core mechanisms might not be useful diagnostically, and so the tests wont be for them, but they might still be useful for considering targeted interventions.

 

I feel that an even stronger argument for ME being reversible is temporary remission. I had several, more frequently at the start, with the last one maybe in year 5 or so, with none in the last 14 or so years, alas. These were an abrupt switch from full ME to apparently fully healthy again over a period of minutes, and lasting for hours, then an abrupt switch back to regular ME symptoms. To me that suggests the core problem exists in a small volume of the brain. I triggered remission with prednisone, T2 (3-5 diiodothyronine) and cumin (cuminum cyminum, probably the cuminaldehyde), and several remissions had undetermined triggers. These triggers worked the first few times, then stopped working ever again.

I don't think PEM should be an absolute criteria. It's a complex disease with lots of variability, so I would expect some people to have minimal PEM symptoms, or high triggering thresholds, or not have it at all. My physically-induced PEM had non-standard triggering. A 20 km bike ride wouldn't trigger PEM, but climbing a ladder once would, or a few seconds washing a window would; it depended on how the muscles were used. I managed to block my physically-induced PEM with cumin, and after a year or two of that, I no longer get PEM anymore from physical activity. I still get it from cerebral exertion, and I still have my other ME symptoms, so curing one symptom doesn't mean that I don't still have ME.

I may have had PEM in my first few years of ME, but I didn't recognize it as PEM. I had better and worse periods of symptoms with no obvious explanation, so PEM might have been in there. I think it was around year 10 that I read the Canadian criteria for ME and realized that I fit that, and learned about PEM and realized that explained my pattern of "feel better, go for long bike ride, feel worse 24 hrs later". We don't have a clinical measurement for PEM.

 

Might be reversible somewhat. A bunch of us got a lot of relief from Abilify—Martin (paused_me) went from severe bedbound to going to work. I don’t think you would get a similar response in MS from any of their meds.

I agree with the discussion of PEM. I’m not really much an acute PEM person but I’m sure I have this syndrome. But I don’t want this thread to devolve into a you don’t have PEM, you are not one of us thread.

I hope I won’t be left behind....But hopefully a biomarker might sort this out.

 

I had about a five year stretch where this happened over and over. They nearly always lasted about six hours for me, but others seem to have different time frames. On one occasion I went from barely able to walk, very slowly, to being able to run at a moderate pace for about twenty minutes. The next morning the improvement was gone and I had trouble walking. On another occasion I went from struggling with a calculator (physical chemistry problems) to being easily able to do math and a lot of it in my head. Then my math skills went away. The best ever improvement was in the hours before a major exam at university, and my brain was switched on for the whole thing. Sadly I have not had one of these spontaneous remissions for most of twenty years now. I tried everything I could to try to replicate the improvement, but nothing worked.

 

Researchers should put out a call for anyone who is able to trigger temporary remissions reliably, even if it's only for a few times. Get the patient in a lab, do extensive testing, trigger the remission, then redo the tests and see what's changed (and redo again when switched back out of remission). I would have endured all that testing if that had been available when I discovered T2 would trigger it.

 

Temporary remissions do indeed give us some hope that this thing is not permanent and irreversible (eg. like brain damage). Unfortunately I can't say I've ever experienced a full 100% remission, but I have experienced great improvements, eg. sometimes when having a cold I feel much better for the duration of it. The one time I experienced something that felt like close to 100% remission was when I was very sleep deprived (24 hr + without sleep) and in a stressful situation. For a few hours, I just felt it was gone. But then again, I wonder, was this a remission or just a ton of stress hormones masking my symptoms?