Patient and Public Involvement opportunities in ME/CFS and other research

Thank you very much for your important question. Not at this stage of the project due to the capacity of the research team, but we are aware that this is also a very important area of research and hope to consider going forward.

*Edit* I am revisiting this with the research team as I want to make our research as inclusive as possible -- we are a small team but I know the value of ensuring as many people are represented as possible. We need to be pragmatic, but will get our thinking caps on as how best to proceed.

 

I hope you and your team can make inclusion happen.

 

Hi all,

I'm a new PhD student with Prof. Chris Ponting at the University of Edinburgh, looking for PPI participants.

The project is to follow up the findings of a case study that I published last year, doi: 10.1186/s12967-023-04711-5, which describes a patient with a severe ME-like condition whose unusual reaction to certain steroid treatments inspired a novel hypothesis involving excessive activation of the gamma amino butyric acid type A receptor (GABAAR) by neuroactive steroids. Subsequent genetic analysis identified a structural variant that affects the exact pathway implicated by the hypothesis. Transcriptional and biochemical studies suggested that the enzymes affected by the variant are indeed altered in a way that closely matches the clinical presentation.

I now intend to assess the frequency of variants in the same genes in a large population of patients relative to healthy controls, conduct RNA sequencing on samples from the original patient and (if funding allows) from other patients and controls, and analyse the blood concentrations of the relevant steroids in patients and controls, to find out if the genetic and biochemical abnormalities described in the case study really do seem to cause some cases of ME. If they do, then these abnormalities could be a diagnostic test that would identify a subset of patients who might respond to treatments suggested by the aetiology. Parts of the study already have funding and I am looking into possible funding opportunities for the rest.

For PPI:

• Looking for 2 PPI participants.
• Engagement would be an initial video call of up to one hour, which would be in the mid-late afternoon, then probably two one-hour video calls per year. There may also be occasional contact by email, and it is likely that some paperwork would be sent for review ahead of the online meetings. The precise level and methods of engagement could be agreed at the first meeting then adjusted as we go, depending on the health/ability of the participants.
• Panel members will be reimbursed for their time, both for the video calls and for reviewing the paperwork, in line with UK PPI standards.

If you are interested then please DM me through this forum or email chris.ponting@ed.ac.uk, and I am obviously happy to answer any questions about the project or the PPI.

Julia

 

So pleased to hear you're doing this research, Julia.

Common steroid meds cause severe ME in me, and I've often wondered about other people—especially if the link is less obvious because they take them more frequently than I did. Although the case you published is very specific, it's good to have people working on it in case there's something hiding here that might affect others.

I'd be useless at PPI, unfortunately, but I hope you find a couple of people with working brains!

 

Thanks Kitty, that's really good of you to say. Firstly: I'm sorry you have that experience, but also: that's really interesting! Might you be willing (and able) to tell me more? It's probably not the same thing I'm investigating but it could be relevant to the study. Obviously only if you are happy to share that information though. I can DM you my email address if appropriate, I just didn't want to put it on a public forum for now.

 

Hi Nellie, certainly if someone would like to participate but is unable to manage a call then we could see how to work it in writing. It would be good to make sure that severely affected voices are heard. Also, if there are people who would like to join a call, and could manage something but not the full hour, then we could look at options like keeping the calls shorter, speaking more softly and slowly, or whatever else might enable them to take part in a way that is manageable.

 

Yes, that's fine. I've described it here before, it's nothing especially sensitive.

It was caused by common-or-garden steroids used for asthma and ear problems. Although they're topical steroids you do ingest some of the drug, especially with the liquid type that's squirted up the nose.

I only need occasional asthma treatment and the same went for recurrent labyrinthitis, so it took ages to realise that all the severe crashes I'd had coincided with taking these meds. If I needed to take the nasal spray long term because I couldn't clear the labyrinthitis, I'd end up confined to bed (normally I was only mildly or moderately affected), sleeping for 16 – 20 hours a day. This would go on for months, and even after I'd stopped the meds it would take ages to recover.

At the time I described it as severe ME, but I now know that although I was very unwell, it wasn't really the same thing. I have noise and light sensitivity, sure, but it didn't escalate the way it does in severe ME to the point where people have to lie in darkened rooms wearing ear defenders. I didn't avoid sitting up in bed because it made me feel extremely ill, I was horizontal because I couldn't stay awake.

I once asked a GP if it was possible the medications were causing this, but they said it wasn't. I finally fathomed it out when I started going suddenly dizzy with the onset of labyrinthitis, unearthed an old nasal spray that was still just about in date, and started using it. I'd been in good shape for some time, but within a day and a half of starting the spray I couldn't stay awake. I binned it for good at that point.

It doesn't sound at all like the case you studied, Julia, but it is ... weird. It's definitely repeatable, as I find out a couple of years ago when I had the worst dose of asthma for ages. I only took a fraction of the steroid doses I was prescribed and I did manage to stay out of bed, but I was still flatlining.

There could be any number of reasons it happens, of course, and I've no way of knowing one way or the other. My ME started at age 17 and I think I only took asthma steroids once before that, but they didn't cause this response. It seems either to be a post-ME thing, or a post-menarche thing (mine was unusually late, and the two things coincided).

If you need to ask anything else, by all means DM me your email address.

 

Thread here
https://www.s4me.info/threads/long-...ere-fatigue-2023-oakley-et.35423/#post-495716

And welcome Julia

 

Definitely weird! I see what you mean that it's different, but actually there are some striking parallels. The patient's "unusual reaction" was that oral hydrocortisone (the same class of steroid (glucocorticoid) as used for asthma) left her unable to stay awake. As if she had taken a sedative. It started on the second day of treatment and continued until she stopped taking it. It sounds like a different pattern, and of course the different steroids all have slightly different effects and different durations of action, but it does seem like it could have a similar underlying cause. Plus the patient's steroids were oral, and it is known that nasal administration of various medications can have a particularly pronounced effect on the brain. It could all be linked to menarche too, due to the way reproductive hormones are metabolised and the effect they have on expression of the relevant enzymes. You're the first person I've heard of apart from the patient for whom glucocorticoids were sedating!

 

Thanks!

 

Yes, definitely. I don't have any endocrine issues, and I do seem to have underlying ME that's not related to the steroid meds. I'm as sure as I can be that it wasn't triggered by taking them.

Nice to know I'm not uniquely odd!

I wonder if the fact that I had ME to start with, and was only just coping energy-wise, was partly what made it show up so starkly. With the asthma meds at least, I think I'd have been able to carry on if I'd been healthy; I might have put feeling very tired and sluggish down to the fact the asthma was keeping me awake at night. It wouldn't surprise me if there were other affected asthma patients who haven't joined the dots.

The nasal spray is different, it seems to have a much stronger effect. As a young healthy person I'd have been better equipped to cope with it, but I couldn't have missed the effect. That medication might be taken by far fewer people (especially for several months at a time) than asthma preventers, though, so perhaps it's less likely to be reported.

Anyway, I hope the research goes well, it's an intriguing finding. By all means DM me if you can't find both PPI participants; I could potentially do it, I just know there are people who'd do a much better job because they're less cognitively impaired than I am. I struggle with verbal articulacy in particular, but writing's not much better! It's taken me 50 minutes to draft this.

 

Hello Julie O, I wonder what your sources are for your statement that nasal medications (I'm assuming you include nasal steroids) can have a "particularly pronounced effect on the brain."

I have moderate to severe fibromyalgia and some symptom overlap with ME/CFS
x28 yr duration.

My use of continuous nasal steroids for non-allergic rhinitis (x 30 years now) preceded the onset at age 46 of fibromyalgia symptoms by about two years. Onset of fibromyalgia symptoms began at age 46, which is common.

Your statement, of course, piques my interest.
Thanks.

 

Thanks Kitty, I will keep you in mind. It really is fascinating and I bet you're right about other people having the same thing but not joining the dots because it's not usually so obviously linked to the medication. And thank you for putting so much effort into writing the reply - I really do appreciate how much of a struggle it can be.

 

Hi Shak8, This review article gives a pretty good overview:
Huang Q. et al. Research progress in brain-targeted nasal drug delivery. Front Aging Neurosci. 2024 Jan 17;15:1341295. doi: 10.3389/fnagi.2023.1341295. I don't know if/how it might relate to fibro - this whole field has barely been considered and I think it warrants more investigation.

 

A reminder of these two opportunities which, I understand, are still looking for PPI representatives.

 

Thanks to everyone - we now have both of the participants for the Edinburgh neurosteroids/genetics PhD study.

 

I thought this was one of the more interesting studies in the last years. I would have applied as PPI representative had I seen this earlier.

 

Hi Hoopoe - thanks! I've asked Chris and we can make it three participants if you'd still like to join us?

 

Sure.