Discussion in 'ME/CFS research news' started by strategist, Jul 1, 2022.
He clarifies that gene product was discovered to be raised in the ME cohort of the NIH intramural study which will be published by 2023.
Processes this gene is involved in
involved_in actin cytoskeleton organization IBA PubMed
involved_in actin filament polymerization TAS PubMed
involved_in cytoskeleton organization IMP PubMed
involved_in lamellipodium assembly IEA
involved_in modification of postsynaptic actin cytoskeleton IEA
involved_in oligodendrocyte development IEA
involved_in positive regulation of Arp2/3 complex-mediated actin nucleation IBA PubMed
involved_in positive regulation of myelination IEA
involved_in protein-containing complex assembly TAS PubMed
involved_in regulation of cell shape
Taken from https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=10810
According to the information on that page, the expression of that gene is highest in the brain.
How is the WAVE3 gene connected to the mitochondria? The amount of the gene product is raised in ME/CFS patients, and that then influences the mitochondria somehow?
It seems like more and more researchers are interested in the mitochondria (& looking at muscle function / muscle biopsies) now in ME.. I’m glad that this avenue is being seriously looked at.
My understanding is that the link to mitochondria is autophagy (degradation of damaged cellular components) and maybe also organization of the mitochondrial network. It also has various other roles.
But this is a complicated topic and I may be misunderstanding. I'll have to read more. It's possible that the NIH knows something that we don't.
On further reading, a picture emerges of WAVE3 being part of one of several protein complexes that physically attach mitochondria to the endoplasmatic reticulum. This would also allow mitochondria and the ER to communicate with each other. This has been studied in cancer.
There's truly a first time for everything.
No, seriously though, this would literally be the first time.
Any idea about what tissue the gene expression assay was performed on? Were fat tissue and muscle biopsies included in the NIH intramural study?
Wasn't the numbers of patients recruited to this study tiny i.e. around 35 over 5 years?
If it was as low as that wouldn't finding a significant gene product in such a tiny cohort be highly unlikely?
Sorry may be talking nonsense but I really don't trust Nath or Walitt.
@John Mac If my memory serves right, the investigators had issued an update to the participants in early 2020 noting that they had found evidence of mitochondrial dysfunction with the Seahorse assay. The number of patients is indeed too low to pinpoint a specific gene, but their results may point towards it possibly having a role in ME/CFS.
Edit: it is the expression of the gene that is upregulated here; this is not the same as identifying variants of the gene (which is the goal of a GWAS study). I don’t know whether assessing upregulation reliably requires as many patients as for a GWAS, i.e. at least 10.000 patients.
Increased expression of this protein seems hard to interpret because it's involved in so many different things. But that the NIH is doing a mitochondrial study led by a cancer researcher suggests that they might be thinking that the interaction between WAVE3 and mitochondria is the most promising area. There also is some discussion of developing drugs that target WAVE3 to treat cancer. Maybe that's the kind of drug trials Dr Nath is expecting?
Sounds like they found elevated WASF3 protein in muscle.
A bit more information on what the WAVE3 gene does in the cell besides having something to do with mitochondria.
It's part of a protein family that is also involved in cell movement, which involves restructuring of the cytoskeleton. I'm not entirely sure but believe that cell adhesion and cadherins, Wnt signaling and ephrine-eph signaling are also involved in cell movement according and these have been found to be abnormal in ME/CFS in some studies. Maybe a coherent picture is finally starting to emerge?
@strategist Regarding the title of the thread, Brian Vastag incorrectly wrote that the NIH would perform a muscle biopsy; they will only do an “optional biopsy of the skin” for this study. Muscle biopsies were already done during the intramural study.
If this is the big breakthrough, why only 12 patients? Why not confirm it on all the patients enrolled?
Only 12 patients = pilot study or proof of concept.
The answer is usually money when it comes to this disease, but let's hope they're just incredibly confident about the effect size this time!
This is what i found. WAVE3 is also known as WASF3. Study from 2011
Source : https://pubmed.ncbi.nlm.nih.gov/21584188/
Does the WAVE 3 gene have anything to due with the deformability of red blood cells?
[It's not helping my search that "WAVE 3" is also a television news station in Louisville Kentucky. ]
WAVE3 aka WASF3 appears to be predominantly a central nervous system gene. It's expression is mainly found in those tissues according to RNA expression data and protein expression data.
( from https://www.proteinatlas.org/ENSG00000132970-WASF3/tissue)
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