People with myalgic encephalomyelitis/chronic fatigue syndrome can wait years for diagnoses; biomolecular tests are finally in development. https://www.drugdiscoverynews.com/blood-tests-for-chronic-fatigue-syndrome-15723
Janet Dafoe announced at a May 2016 Millions Missing rally that "we are only months away from a biomarker".
Is it though? Many illnesses have biomarkers w/o cures. Disease management with medications yes, but not cures.
Merged thread The article has interviews with Ron Davis, Maureen Hanson and Alain Moreau Quote: While there’s currently no simple biological marker for ME/CFS — patients’ routine laboratory tests generally fall within normal values — Hanson emphasized that patients with ME/CFS are biologicallydistinguishable from healthy people. Patients on average show differences in the composition and function of their gut microbiomes, plasma metabolic profiles, autoimmune gene expression, and immune cell function (9–12). “One problem with developing a marker is that there are lots of differences between individuals,” she said. “It could be that there's a single underlying cause [of the disease], but people's own genetics cause the manifestation of the illness to be different.” https://www.drugdiscoverynews.com/blood-tests-for-chronic-fatigue-syndrome-15723
I thought Hanson's view that you don't need biomarkers to have drug trials was interesting. I assume that you do have to have evidence to support the hypothesis that the drug will work? I'm hoping that GWAS will provide clues but I reckon that with a heterogeneous population it may take a number of large GWAS studies - DecodeME may not (itself) be large enough. In Alzheimer's it took large data sets [much larger than DecodeME] to find the second & third significate genes - & dementia may be less heterogeneous than ME! Still, found Hanson's views re using drug trials, as a way to make progress, interesting & the example of depression seemed valid --- although the effectiveness of the approved (depression) medications is disputed! EDIT - I'm hoping that large GWAS studies might provide some insight e.g. even if a gene doesn't initially reach significance then it may still provide support for a particular drug/intervention. @Simon M - worth pushing this as a +ve for GWAS i.e. even if genes don't initially meet test for significance the data can be used to assess drugs etc?
That's a good question. Is known efficacy of a drug on a symptom enough evidence? Presumably that's how at least some drugs are applied in trials. It doesn't seem unusual for it to remain unclear how some drugs work even decades after they were introduced, so the relationship between drug and disease isn't necessarily straightforward. I suspect a lot of discoveries are/were accidental (or serendipitous, to put a slightly more professional-sounding slant on it).
Yes. Essentially all treatments for rheumatoid arthritis were serendipitous until the 1990s when we began to understand mechanisms. You need either a mechanism rationale or some pragmatic evidence that suggests an effect to justify most trials.
Pretty decent article. More rigorous than a typical popular article, as it has references. Author actually interviewed people with actual expertise versus interviewing people with large Twitter accounts.
Jonathan --- "You need either a mechanism rationale or some pragmatic evidence that suggests an effect to justify most trials." Yea so maybe something like someone with MECFS was treated with X and it appeared to improve, rituximab comes to mind. Also, discussion re TPPP gene, wouldn't necessarily turn up accidentally (since there are no drugs and no biomarker) but as per discussion here* identification via GWAS may be a route to identify potential targets for drugs. EDIT - another drug that comes to mind is Lithium which is used in manic depression. In the last few years I noticed that researchers had discovered that it changed the shape of a protein - assumed to be its mode of action. So efficacy and mechanism can be discovered decades apart. *https://www.s4me.info/threads/genet...ential-risk-loci-2022-hajdarevic-et-al.25070/
The bottom line with prospective markers is that nothing has been properly revisited and validated in publication since the wave of modern biomarker studies began a handful of years ago. We have many papers finding lab differences that can separate already defined clinical groups. That's only step 1. What I hope is that people are going back to the same proposed marker measurements that are published and testing them in larger cohorts and with different methods that are more clinically practical than the expensive and expertise- or instrument-demanding assays that we all usually do in research, but because of the potential IP implications of a blood test it is hard to know what's going on behind the scenes. I guess time will tell. I am aware of one group beyond my own that has interesting findings that are trying to be repeated internationally with different instruments and I wish them the best. Otherwise I am in the dark. I just hope the lack of noise is because of people being cautious with their plans rather than not following things up at all. Maybe not a diagnostic marker but you would need at least some demonstrated basis for underlying mechanism or useful effect. As Jonathan Edwards mentions. I personally would not want to think about trialing a drug on people unless it has been shown to ameliorate an indicative, well-characterised disease phenotype in an accepted disease model. I don't know that anybody has these things yet. My 2c. And this is why we need to measure not one but several things concurrently, and to work on either better subtyping or an increased focus on the unique pattern of the individual. David Putrino and Chris Armstrong are also proponents of these ideas. I think it is the way to go.
This is where any serious research must start. I have no doubt there are already clues in the literature, but they need to be identified and followed up properly. Thanks for engaging here.
