Altered TRPM7-Dependent Calcium Influx in Natural Killer Cells of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients, 2023, du Preez et al

Discussion in 'ME/CFS research' started by Sly Saint, Jun 26, 2023.

  1. Sly Saint

    Sly Saint Senior Member (Voting Rights)

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    Abstract:
    Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling multisystemic condition. The pathomechanism of ME/CFS remains unestablished; however, impaired natural killer (NK) cell cytotoxicity is a consistent feature of this condition. Calcium (Ca2+) is crucial for NK cell effector functions.

    Growing research recognises Ca2+ signalling dysregulation in ME/CFS patients and implicates transient receptor potential ion channel dysfunction. TRPM7 (melastatin) was recently considered in the pathoaetiology of ME/CFS as it participates in several Ca2+-dependent processes that are central to NK cell cytotoxicity which may be compromised in ME/CFS. TRPM7-dependent Ca2+ influx was assessed in NK cells isolated from n = 9 ME/CFS patients and n = 9 age- and sex-matched healthy controls (HCs) using live cell fluorescent imaging techniques. Slope (p < 0.05) was significantly reduced in ME/CFS patients compared with HCs following TRPM7 activation.

    Half-time of maximal response (p < 0.05) and amplitude (p < 0.001) were significantly reduced in the HCs compared with the ME/CFS patients following TRPM7 desensitisation. Findings from this investigation suggest that TRPM7-dependent Ca2+ influx is reduced with agonism and increased with antagonism in ME/CFS patients relative to the age- and sex-matched HCs. The outcomes reported here potentially reflect TRPM3 dysfunction identified in this condition suggesting that ME/CFS is a TRP ion channelopathy.

    https://www.mdpi.com/2218-273X/13/7/1039
     
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  2. John Mac

    John Mac Senior Member (Voting Rights)

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    Yes, but always from the same group of researchers.
     
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  3. Trish

    Trish Moderator Staff Member

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    It would be good to see this work replicated by other teams and with larger samples. Still only 9 patient and 9 controls here. It looks like this is newly collected samples using CCC diagnostic criteria. I don't understand enough about the details to know whether this progresses significantly from what they had found before.
    It's interesting to see the reference to Aripiprazole as a treatment that might be relevant to this finding.
     
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  4. Jaybee00

    Jaybee00 Senior Member (Voting Rights)

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    “Clinical evidence further supports TRPM7 as a potential therapeutic target to improve health outcomes for ME/CFS patients. Aripiprazole is a promising therapeutic agent for the treatment of ME/CFS that is suggested to reduce microglial activation and associated neuroinflammation via TRPM7 [66].”
     
  5. Jaybee00

    Jaybee00 Senior Member (Voting Rights)

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    Doesn’t look like there is good candidate TRPM7 agonist that is selective for this receptor.
     

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