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• W2892468641 abstract "Abstract Introduction Classic Charcot‐Marie‐Tooth (CMT) neuropathies including those with Schwann cell genetic defects exhibit a length‐dependent process affecting the distal axon. Energy deprivation in the distal axon has been the proposed mechanism accounting for length‐dependent distal axonal degeneration. We hypothesized that pyruvate, an intermediate glycolytic product, could restore nerve function, supplying lost energy to the distal axon. Methods To test this possibility, we supplied pyruvate to the drinking water of the Trembler‐J (Tr J ) mouse and assessed efficacy based on histology, electrophysiology, and functional outcomes. Pyruvate outcomes were compared with untreated Tr J controls alone or adeno‐associated virus mediated NT‐3 gene therapy (AAV1.NT‐3)/pyruvate combinatorial approach. Results Pyruvate supplementation resulted increased myelinated fiber (MF) densities and myelin thickness in sciatic nerves. Combining pyruvate with proven efficacy from AAV1.tMCK.NT‐3 gene therapy provided additional benefits showing improved compound muscle action potential amplitudes and nerve conduction velocities compared to pyruvate alone cohort. The end point motor performance of both the pyruvate and the combinatorial therapy cohorts was better than untreated Tr J controls. In a unilateral sciatic nerve crush paradigm, pyruvate supplementation improved myelin‐based outcomes in both regenerating and the contralateral uncrushed nerves. Conclusions This proof of principle study demonstrates that exogenous pyruvate alone or as adjunct therapy in Tr J may have clinical implications and is a candidate therapy for CMT neuropathies without known treatment." @default.
• W2892468641 created "2018-10-05" @default.
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• W2892468641 date "2018-09-21" @default.
• W2892468641 modified "2023-10-14" @default.
• W2892468641 title "Efficacy of exogenous pyruvate in Trembler^J mouse model of Charcot-Marie-Tooth neuropathy" @default.
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• W2892468641 doi "https://doi.org/10.1002/brb3.1118" @default.
• W2892468641 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6192403" @default.
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