Facioscapulohumeral Dystrophy (FSHD)

@Hutan,

Good to hear! Peter Jones is such a knowledgeable and enthusiastic communicator.

I think I will take @Daisybell's recommendation about his podcast and give it a listen. it would be interesting to hear him talk about the genetic/inherited links he is seeing or not seeing.

 

@Daisybell a recent paper potentially of interest, in case you haven't seen it —

Identification of circulating miRNAs differentially expressed in patients with Limb-girdle, Duchenne or facioscapulohumeral muscular dystrophies (2022, Orphanet Journal of Rare Diseases)

 

Yes, and offers free testing world-wide – that's such a great facility to include in their study.

 

Ive been listening to the podcasts for some time now and I keep thinking i understand the genetics and epigenetics and then I realise I don’t really!
My methylation levels for the implicated region are 8% which apparently is a clear indication that the gene is switched on rather than being off as it should be…
It’s all a bit of a bummer really.
And the complexity of the issue means that treatment is difficult.

Hi everyone by the way!

 

@Hutan, do you think it is possible that the UK DecodeME project might eventually lead to the pursuit of avenues like this? I am not suggesting we know anything yet, but is this a example of genetic hints leading to at least a diagnostic methodology?

 

I had a holter monitor on for a couple of days last week. I’m trying to get to the bottom of whether my issues with my heart rate are linked to my FSHD. The health system is trying to find out whether I am making the issues up or not….!
Anyway, I bent over to put on my socks and my heart rate (according to my iWatch) went up to 167, and stayed like that for a couple of minutes. Hopefully that will be enough evidence to a) convince them that I’m not imagining it and b) diagnose what is going on.

Fun and games!

 

Hi everyone.
There is a clinical trial for an anti-sense RNA treatment for FSHD which has been granted approval in NZ - I am very much hoping that I can be part of it…. Even if I get the placebo! At least that way, if the treatment does work, I will have perhaps a chance at getting the drug in the future. The drug being tested is called Aro-Dux 4. The link to the trial info is here
https://clinicaltrials.gov/study/NCT06131983

 

I think the trial is happening here because there is a good neuromuscular disease registry which is run from Auckland. And possibly because we can’t sue if anything goes wrong???!! They only need a small number of participants, and because of the nature of the treatment, no healthy volunteers.
It’s been tested in mice, but there is no large animal model for testing FSHD interventions so the next step is straight to humans.

 

Another preprint for you @Daisybell

A novel family of lncRNAs relate facioscapulohumeral muscular dystrophy to nucleolar architecture and protein synthesis
Valentina Salsi; Francesca Losi; Bruno Fosso; Marco Ferrarini; Sara Pini; Marcello Manfredi; Gaetano N. A. Vattemi; Tiziana E. Mongini; Lorenzo Maggi; Graziano D. Pesole; Anthony Henras; Paul D. Kaufman; Brian McStay; Rossella Ginevra Tupler

Facioscapulohumeral muscular dystrophy (FSHD) is a hereditary myopathy linked to deletions of the tandemly arrayed D4Z4 macrosatellite repeats at human chromosome 4q35. These deletions accompany local chromatin changes and the anomalous expression of nearby transcripts FRG2A, DBET, and D4Z4.

We discovered that FRG2A is one member of a family of long non-coding RNAs (lncRNA) expressed at elevated levels in skeletal muscle cells in an individual-specific manner. We found that FRG2A lncRNA preferentially associates with rDNA sequences and centromeres, and also promotes the three-dimensional association of centromeres with the nucleolar periphery in FSHD samples. Furthermore, we demonstrate that the elevated FRG2A expression in cells from FSHD patients reduces rDNA transcription and protein synthesis.

Our results frame a new disease model in which elevated lncRNAs expression mediated by deletions of D4Z4 macrosatellite repeats leads to a diminished protein synthesis capacity, thereby contributing to muscle wasting.


Link | PDF (Preprint: BioRxiv) [Open Access]

 

Thanks @SNT Gatchaman - that makes my head hurt!!! I’ve sent it on to Prof Jones in Reno… If he thinks it is interesting, he might explain to us over Spotify!

 

The drug development companies certainly like an easy way to get hold of participants…

 

Hundreds of children born with a degenerative muscle-wasting disease are to be offered a new drug on the NHS that can slow the deadly condition’s progression.

Children with muscle-wasting disease to be offered new NHS drug

 

It does seem that drug trials are beginning for various forms of muscular dystrophy.

A ‘lack of progress’ update on my situation…
At this point, i have been told I am not being considered for the FSHD drug trial in this country. Apparently I am not sufficiently affected.
I haven’t actually seen the neurologist since my initial appointment where he confirmed that I do have FSHD and have some symptoms. That was over 2 years ago. I went to see my GP the other day and she has referred me back to Neurology. I am presuming that the one year follow up that was planned after my initial appointment has just been scrubbed. I don’t know whether the system just removes people from the waitlist if the appointments are so delayed… it certainly seems like things are not working well in the health system at the moment. But I am not prepared to just put up with being told that I am too mild for the trial if in fact the specialist has only seen me once 26 months ago.