#59: Good Gene Vs Bad Gene
Hello Long Hauler fam,
☀️ Here are 3 of the more promising research findings from the last month, plus 1 thought and 1 question.
3 IDEAS FROM RESEARCH
I.
The biggest update this month is not just “more genetics”. It is genetics getting closer to treatment.
The UK government is backing SequenceME, a major project that will sequence the full (complete! total!) genomes of up to 6,000 people with ME/CFS. The aim is to find biological patterns that could lead to better diagnostics, clearer subtypes, and eventually targeted treatments.
This builds on the earlier DecodeME work, which found genetic signals linked to immune function, infection response, nervous system biology, and chronic pain.
That connects so neatly with the fascinating work done by PrecisionLife which HealthRising covered recently. One of the most interesting bits is PL’s focus on protective mechanisms. In plain English: they are not only asking “what makes people ill?” They are also asking “who are the people who have the ‘bad genes’ but didn’t get sick? What genes protected them? And what clues does that give for developing treatments?”
If a pathway seems to protect people, researchers can ask whether a drug could strengthen that pathway, mimic it, or reduce the opposite damaging process.
HealthRising notes that PrecisionLife has already used this kind of approach in another disease, ALS, where protective genetic clues are helping point towards possible treatment strategies. They have also identified candidate treatments for ME/CFS and Long Covid and are sharing them with research groups(!)
This is still early. But it is a better kind of early: not “we found a vague association”, but “we found pathways that might be testable”.
II.
A small controlled pilot suggests ear-based vagus nerve stimulation is tolerated for Long Covid, but while there were improvements, they were no better than the placebo group..
This is called transcutaneous auricular vagus nerve stimulation, or taVNS. It is a non-invasive form of stimulation delivered through the ear.
The promising part is that this was not just an anecdote. It was a randomised, sham-controlled pilot study, which means people were compared against a fake-treatment control.
Even though the results were not particularly promising, it is still great to see proper, high quality tests being done that help us understand better what works and what doesn’t. Of course, until we have proper subgroups it might be very hard to get positive results (it might help some but not others), unless trials are sufficiently large.
Source: PubMed
III.
A new Long Covid paper strengthens the case that PEM should be treated as central, not secondary.
The study found that post-exertional malaise frequency and severity were strongly linked to worse quality of life in Long Covid (mic drop).
That sounds obvious to patients, but it matters scientifically. It pushes back against the idea that Long Covid fatigue is just generic tiredness or deconditioning.
Why it matters:
PEM-aware care should be built into Long Covid support
Trials should measure PEM, not just broad fatigue (you’d be amazed how many haven’t in the past)
Treatment plans that ignore PEM may miss the main driver of disability
This is one of those findings that feels less flashy than a drug trial, but it could improve both research design and patient care.
Source: Springer open-access paper
1 THOUGHT
How cool to think about genes as not just disease mechanisms but protective mechanisms - not just what makes us sick but what makes us healthy! It appeals to the optimist in me, as does the march towards more precision and targeted meds for the (still murky but emerging) different sub groups.
Source: All of the above
1 QUESTION FOR YOU
If you were a scientist (or if you are!): what would you want to study right now?
puppy p.s. Buds
[alt text: Whisky and Monty have moved in together and when not chewing each other’s ears are sunning themselves out back]
Wishing you a peaceful week,
Tom and Whisky
☺️
This newsletter is and always will be free.
🌟 If you would like to support my local charity ME/CFS Canterbury, you can by upgrading to paid (100% of donations go to them - they are amazing and offer specialist nurse services amongst other things) 🌟
my apologies about the TaVNS - that was a bad oversight on my part. i've corrected the blog. it is interesting to think how much proper subtyping would help with discovering any potential treatments – and is doing studies without it actively causing harm (by potentially discrediting helpful treatments)?
Proper PEM and mecfs screening would be huge. The treatME survey did subtype based on symptoms but patient reported outcomes are dubious at best.
I think getting a null result from a popular anecdotal treatment is still helpful in knowing what doesn't work.
Until we get sequence ME data or some other strong pathophysiological biomarkers we won't know. Hopefully, funding will shift into that area of discovery!