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No therapy is available. PXT3003 is a low\u2010dose combination of baclofen, naltrexone, and sorbitol which has been shown to improve disease symptoms in\n                    <jats:italic>Pmp22<\/jats:italic>\n                    transgenic rats, a bona fide model of CMT1A disease. However, the superiority of PXT3003 over its single components or dual combinations have not been tested. Here, we show that in a dorsal root ganglion (DRG) co\u2010culture system derived from transgenic rats, PXT3003 induced myelination when compared to its single and dual components. Applying a clinically relevant (\u201ctranslational\u201d) study design in adult male CMT1A rats for 3\u00a0months, PXT3003, but not its dual components, resulted in improved performance in behavioral motor and sensory endpoints when compared to placebo. Unexpectedly, we observed only a marginally increased number of myelinated axons in nerves from PXT3003\u2010treated CMT1A rats. However, in electrophysiology, motor latencies correlated with increased grip strength indicating a possible effect of PXT3003 on neuromuscular junctions (NMJs) and muscle fiber pathology. Indeed, PXT3003\u2010treated CMT1A rats displayed an increased perimeter of individual NMJs and a larger number of functional NMJs. Moreover, muscles of PXT3003 CMT1A rats displayed less neurogenic atrophy and a shift toward fast contracting muscle fibers. We suggest that ameliorated motor function in PXT3003\u2010treated CMT1A rats result from restored NMJ function and muscle innervation, independent from myelination.\n                  <\/jats:p>","DOI":"10.1002\/jnr.24679","type":"journal-article","created":{"date-parts":[[2020,6,26]],"date-time":"2020-06-26T04:31:07Z","timestamp":1593145867000},"page":"1933-1952","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Synergistic PXT3003 therapy uncouples neuromuscular function from dysmyelination in male Charcot\u2013Marie\u2013Tooth disease type 1A (CMT1A) rats"],"prefix":"10.1002","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8210-9277","authenticated-orcid":false,"given":"Thomas","family":"Prukop","sequence":"first","affiliation":[{"name":"Department of Neurogenetics Max Planck Institute of Experimental Medicine G\u00f6ttingen Germany"},{"name":"Institute of Clinical Pharmacology University Medical Center G\u00f6ttingen G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Wernick","sequence":"additional","affiliation":[{"name":"Department of Neurogenetics Max Planck Institute of Experimental Medicine G\u00f6ttingen Germany"},{"name":"Department of Clinical Neurophysiology University Medical Center G\u00f6ttingen G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydie","family":"Boussicault","sequence":"additional","affiliation":[{"name":"Pharnext Issy\u2010Les\u2010Moulineaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Ewers","sequence":"additional","affiliation":[{"name":"Department of Neurogenetics Max Planck Institute of Experimental Medicine G\u00f6ttingen Germany"},{"name":"Department of Clinical Neurophysiology University Medical Center G\u00f6ttingen G\u00f6ttingen 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University Medical Center G\u00f6ttingen G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Linhoff","sequence":"additional","affiliation":[{"name":"Department of Neurogenetics Max Planck Institute of Experimental Medicine G\u00f6ttingen Germany"},{"name":"Department of Clinical Neurophysiology University Medical Center G\u00f6ttingen G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alonso","family":"Barrantes\u2010Freer","sequence":"additional","affiliation":[{"name":"Department of Neuropathology University Medical Center Leipzig Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Bartl","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurophysiology University Medical Center G\u00f6ttingen G\u00f6ttingen 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