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Preclinical Research in McArdle Disease: A Review of Research Models and Therapeutic Strategies.

ABSTRACT: 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.

SUBMITTER: Villarreal-Salazar M

PROVIDER: S-EPMC8774685 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Preclinical Research in McArdle Disease: A Review of Research Models and Therapeutic Strategies.

Villarreal-Salazar Mónica M Brull Astrid A Nogales-Gadea Gisela G Andreu Antoni L AL Martín Miguel A MA Arenas Joaquín J Santalla Alfredo A Lucia Alejandro A Vissing John J Krag Thomas O TO Pinós Tomàs T

Genes 20211228 1

McArdle disease is an autosomal recessive disorder of muscle glycogen metabolism caused by pathogenic mutations in the <i>PYGM</i> 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 mode ...[more]

PMID: 35052414

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Project description:Introduction and methodsMyophosphorylase deficiency, also known as McArdle disease or Glycogen Storage Disease type V (GSD-V), is an autosomal recessive metabolic myopathy that results in impaired glycogen breakdown in skeletal muscle. Despite being labelled as a "pure myopathy," cardiac involvement has been reported in some cases, including various cardiac abnormalities such as electrocardiographic changes, coronary artery disease, and cardiomyopathy. Here, we present a unique case of a 72-year-old man with GSD-V and both mitral valvulopathy and coronary artery disease, prompting a systematic review to explore the existing literature on cardiac comorbidities in McArdle disease.ResultsOur systematic literature revision identified 7 case reports and 1 retrospective cohort study. The case reports described 7 GSD-V patients, averaging 54.3 years in age, mostly male (85.7%). Coronary artery disease was noted in 57.1% of cases, hypertrophic cardiomyopathy in 28.5%, severe aortic stenosis in 14.3%, and genetic dilated cardiomyopathy in one. In the retrospective cohort study, five out of 14 subjects (36%) had coronary artery disease.Discussion and conclusionDespite McArdle disease primarily affecting skeletal muscle, cardiac involvement has been observed, especially coronary artery disease, the frequency of which was moreover found to be higher in McArdle patients than in the background population in a previous study from a European registry. Exaggerated cardiovascular responses during exercise and impaired glycolytic metabolism have been speculated as potential contributors. A comprehensive cardiological screening might be recommended for McArdle disease patients to detect and manage cardiac comorbidities. A multidisciplinary approach is crucial to effectively manage both neurological and cardiac aspects of the disease and improve patient outcomes. Further research is required to establish clearer pathophysiological links between McArdle disease and cardiac manifestations in order to clarify the existing findings.

Dataset Information

Preclinical Research in McArdle Disease: A Review of Research Models and Therapeutic Strategies.

Publications

Preclinical Research in McArdle Disease: A Review of Research Models and Therapeutic Strategies.

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