Targeted therapies for metabolic myopathies related to glycogen storage and lipid metabolism: a systematic review and steps towards a 'Treatabolome'

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  • dc.contributor.author Manta, Alexander
  • dc.contributor.author Spendiff, Sally
  • dc.contributor.author Lochmüller, Hanns
  • dc.contributor.author Thompson, Rachel
  • dc.date.accessioned 2021-05-19T11:25:00Z
  • dc.date.available 2021-05-19T11:25:00Z
  • dc.date.issued 2021
  • dc.description.abstract Background: Metabolic myopathies are a heterogenous group of muscle diseases typically characterized by exercise intolerance, myalgia and progressive muscle weakness. Effective treatments for some of these diseases are available, but while our understanding of the pathogenesis of metabolic myopathies related to glycogen storage, lipid metabolism and β-oxidation is well established, evidence linking treatments with the precise causative genetic defect is lacking. Objective: The objective of this study was to collate all published evidence on pharmacological therapies for the aforementioned metabolic myopathies and link this to the genetic mutation in a format amenable to databasing for further computational use in line with the principles of the "treatabolome" project. Methods: A systematic literature review was conducted to retrieve all levels of evidence examining the therapeutic efficacy of pharmacological treatments on metabolic myopathies related to glycogen storage and lipid metabolism. A key inclusion criterion was the availability of the genetic variant of the treated patients in order to link treatment outcome with the genetic defect. Results: Of the 1,085 articles initially identified, 268 full-text articles were assessed for eligibility, of which 87 were carried over into the final data extraction. The most studied metabolic myopathies were Pompe disease (45 articles), multiple acyl-CoA dehydrogenase deficiency related to mutations in the ETFDH gene (15 articles) and systemic primary carnitine deficiency (8 articles). The most studied therapeutic management strategies for these diseases were enzyme replacement therapy, riboflavin, and carnitine supplementation, respectively. Conclusions: This systematic review provides evidence for treatments of metabolic myopathies linked with the genetic defect in a computationally accessible format suitable for databasing in the treatabolome system, which will enable clinicians to acquire evidence on appropriate therapeutic options for their patient at the time of diagnosis.
  • dc.description.sponsorship AM received a Summer Studentship stipend from the Faculty of Medicine at the University of Ottawa. HL receives support from the Canadian Institutes of Health Research (Foundation Grant FDN-167281), the Canadian Institutes of Health Research and Muscular Dystrophy Canada (Network Catalyst Grant NG2-170044 for NMD4C), the Canada Foundation for Innovation (CFI-JELF 38412), and the Canada Research Chairs program (Canada Research Chair in Neuromuscular Genomics and Health, 950-232279). RT receives support from the Canadian Institutes of Health Research (postdoctoral fellowship award MFE-171275). This review is part of the Solve-RD treatabolome initiative. The Solve-RD project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 779257
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Manta A, Spendiff S, Lochmüller H, Thompson R. Targeted therapies for metabolic myopathies related to glycogen storage and lipid metabolism: a systematic review and steps towards a 'Treatabolome'. J Neuromuscul Dis. 2021;8(3):401-417. DOI: 10.3233/JND-200621
  • dc.identifier.doi http://dx.doi.org/10.3233/JND-200621
  • dc.identifier.issn 2214-3599
  • dc.identifier.uri http://hdl.handle.net/10230/47615
  • dc.language.iso eng
  • dc.publisher IOS Press
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/779257
  • dc.rights © 2021 A. Manta et al. This is an Open Access article distributed under the termsof the Creative Commons Attribution-NonCommercial License (CC BY-NC 4.0)
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri https://creativecommons.org/licenses/by-nc/4.0/
  • dc.subject.other Genètica
  • dc.subject.other Músculs -- Malalties
  • dc.subject.other Farmacologia
  • dc.title Targeted therapies for metabolic myopathies related to glycogen storage and lipid metabolism: a systematic review and steps towards a 'Treatabolome'
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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