The 12th Invest in ME Research Conference June, 2017, Part 2
MEMum presents the second article in a series of three about the recent 12th Invest In ME International Conference (IIMEC12) in London.
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New research on brain mitochondria

Discussion in 'Latest ME/CFS Research' started by Janice Hargreaves, Jul 16, 2017.

  1. Janice Hargreaves

    Janice Hargreaves

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  2. hixxy

    hixxy Senior Member

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    You haven't linked to anything.
     
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  3. Janice Hargreaves

    Janice Hargreaves

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    Ooooooops, this is what I meant
    Ann Neurol. 2017 May;81(5):641-652. doi: 10.1002/ana.24922. Epub 2017 May 4.
    Deoxycytidine and Deoxythymidine Treatment for Thymidine Kinase 2 Deficiency.

    Lopez-Gomez C1, Levy RJ1, Sanchez-Quintero MJ1, Juanola-Falgarona M1, Barca E1,2, Garcia-Diaz B1,3, Tadesse S1, Garone C1,4, Hirano M1.
    Author information
    Abstract
    OBJECTIVE:
    Thymidine kinase 2 (TK2), a critical enzyme in the mitochondrial pyrimidine salvage pathway, is essential for mitochondrial DNA (mtDNA) maintenance. Mutations in the nuclear gene, TK2, cause TK2 deficiency, which manifests predominantly in children as myopathy with mtDNA depletion. Molecular bypass therapy with the TK2 products, deoxycytidine monophosphate (dCMP) and deoxythymidine monophosphate (dTMP), prolongs the life span of Tk2-deficient (Tk2-/- ) mice by 2- to 3-fold. Because we observed rapid catabolism of the deoxynucleoside monophosphates to deoxythymidine (dT) and deoxycytidine (dC), we hypothesized that: (1) deoxynucleosides might be the major active agents and (2) inhibition of deoxycytidine deamination might enhance dTMP+dCMP therapy.
    METHODS:
    To test these hypotheses, we assessed two therapies in Tk2-/- mice: (1) dT+dC and (2) coadministration of the deaminase inhibitor, tetrahydrouridine (THU), with dTMP+dCMP.
    RESULTS:
    We observed that dC+dT delayed disease onset, prolonged life span of Tk2-deficient mice and restored mtDNA copy number as well as respiratory chain enzyme activities and levels. In contrast, dCMP+dTMP+THU therapy decreased life span of Tk2-/- animals compared to dCMP+dTMP.
    INTERPRETATION:
    Our studies demonstrate that deoxynucleoside substrate enhancement is a novel therapy, which may ameliorate TK2 deficiency in patients. Ann Neurol 2017;81:641-652.
    © 2017 American Neurological Association.
     
  4. MeSci

    MeSci ME/CFS since 1995; activity level 6?

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    It's here (abstact only) for anyone who wants to see it or try to get the full text. But I would not attach any significance to an animal study.
     

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