cd23c07acd43078cde5248bafd6d2872 pmc_35052414.pdf dd2a61536017fd66706c261d636ebea3e45d5fda pmc_35052414.pdf 1bc54736261aa64e3a04f5a65a5dad4e950df4628d59a33951b3174e98e698cb pmc_35052414.pdf Title: Preclinical Research in McArdle Disease: A Review of Research Models and Therapeutic Strategies Subject: McArdle disease is an autosomal recessive disorder of muscle glycogen metabolism caused by pathogenic mutations in the PYGM gene, which encodes the skeletal muscle-specific isoform of glycogen phosphorylase. Clinical symptoms are mainly characterized by transient acute “crises” of early fatigue, myalgia and contractures, which can be accompanied by rhabdomyolysis. Owing to the difficulty of performing mechanistic studies in patients that often rely on invasive techniques, preclinical models have been used for decades, thereby contributing to gain insight into the pathophysiology and pathobiology of human diseases. In the present work, we describe the existing in vitro and in vivo preclinical models for McArdle disease and review the insights these models have provided. In addition, despite presenting some differences with the typical patient’s phenotype, these models allow for a deep study of the different features of the disease while representing a necessary preclinical step to assess the efficacy and safety of possible treatments before they are tested in patients. Keywords: McArdle disease; glycogen; glycogen phosphorylase; research models; treatments Author: Mónica Villarreal-Salazar, Astrid Brull, Gisela Nogales-Gadea, Antoni L. Andreu, Miguel A. Martín, Joaquín Arenas, Alfredo Santalla, Alejandro Lucia, John Vissing, Thomas O. Krag and Tomàs Pinós Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Dec 28 10:24:48 2021 CET ModDate: Tue Dec 28 10:30:18 2021 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 18 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 374172 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- CMFVHJ+VnURWPalladioL Type 1 Custom yes yes no 10 0 MCHSAS+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 LAORXT+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 NURLTE+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 RSYDPD+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 36 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 40 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 44 0 KONDUX+EuphemiaUCAS-Bold Type 1C WinAnsi yes yes no 56 0 HIZBRM+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 59 0 UGAYQB+CMSY10 Type 1 Builtin yes yes no 84 0 QDCWHF+EURM10 Type 1 Builtin yes yes no 100 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-05-27 02:51:20 CEST RepresentationInformation: pmc_35052414.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-03-31 12:08:17 CEST Size: 374172 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 540 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Animal Models Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Charolais Cattle Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Ovine Model Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Mouse Model Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Children: Item: Title: Body Mass Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Exercise Intolerance Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Low Survival Rate Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Decreased Glucose and Lactate but Increased CK and Ammonia Blood Levels Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Massive Glycogen Accumulation Disrupts Myofibril Structure Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Fiber Type-Specific Degeneration Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Differential Metabolic Responses among Muscles Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: No Changes in Oxidative Phosphorylation Proteins Levels and Activity Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Increased Markers of Oxidative Stress Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: No Major Changes in the Autophagic Flux and Proteasome System Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: Alterations in CALCIUM Metabolism Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: Disease Progression Differently Affects Distinct Muscles Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: Physiological and Molecular Adaptations to Endurance Exercise Training Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: Zebrafish Model Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Item: Title: Cell Cultures Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@ed9d034 Item: Title: Treatments Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6121c9d6 Children: Item: Title: Upregulation Pygb/Pygl Expression in Mature Skeletal Muscle Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@87f383f Item: Title: Gene Therapy Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4eb7f003 Item: Title: Read-Through Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@eafc191 Item: Title: Critical Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@612fc6eb Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1060b431 Info: Title: Preclinical Research in McArdle Disease: A Review of Research Models and Therapeutic Strategies Author: Mónica Villarreal-Salazar, Astrid Brull, Gisela Nogales-Gadea, Antoni L. Andreu, Miguel A. Martín, Joaquín Arenas, Alfredo Santalla, Alejandro Lucia, John Vissing, Thomas O. Krag and Tomàs Pinós Subject: McArdle disease is an autosomal recessive disorder of muscle glycogen metabolism caused by pathogenic mutations in the PYGM gene, which encodes the skeletal muscle-specific isoform of glycogen phosphorylase. Clinical symptoms are mainly characterized by transient acute “crises” of early fatigue, myalgia and contractures, which can be accompanied by rhabdomyolysis. Owing to the difficulty of performing mechanistic studies in patients that often rely on invasive techniques, preclinical models have been used for decades, thereby contributing to gain insight into the pathophysiology and pathobiology of human diseases. In the present work, we describe the existing in vitro and in vivo preclinical models for McArdle disease and review the insights these models have provided. In addition, despite presenting some differences with the typical patient’s phenotype, these models allow for a deep study of the different features of the disease while representing a necessary preclinical step to assess the efficacy and safety of possible treatments before they are tested in patients. 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