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Therapeutic Aspects in Congenital Myopathies.

Abstract

The congenital myopathies are a genetically heterogeneous and diverse group of early-onset, nondystrophic neuromuscular disorders. While the originally reported "classical" entities within this group - Central Core Disease, Multiminicore Disease, Nemaline Myopathy, and Centronuclear Myopathy - were defined by the predominant finding on muscle biopsy, "novel" forms with multiple, subtle, and unusual histopathologic features have been described more recently, reflective of an expanding phenotypical spectrum. The main disease mechanisms concern excitation-contraction coupling, intracellular calcium homeostasis, and thin/thick filament interactions. Management to date has been mainly supportive. Therapeutic strategies currently at various stages of exploration include genetic interventions aimed at direct correction of the underlying genetic defect, enzyme replacement therapy, and pharmacologic approaches, either specifically targeting the principal effect of the underlying gene mutation, or addressing its downstream consequences more generally. Clinical trial development is accelerating but will require more robust natural history data and tailored outcome measures.

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  • Authors+Show Affiliations

    ,

    Department of Paediatric Neurology, Neuromuscular Service, Evelina's Children Hospital, Guy's and St. Thomas' Hospital NHS Foundation Trust, London, United Kingdom; Randall Division for Cell and Molecular Biophysics, Muscle Signalling Section, London, United Kingdom; Department of Basic and Clinical Neuroscience, IoPPN, King's College, London, United Kingdom. Electronic address: Heinz.Jungbluth@gstt.nhs.uk.

    The Dubowitz Neuromuscular Centre, Developmental Neurosciences Programme, UCL Great Ormond Street Institute of Child Health & Great Ormond Street Hospital for Children, London, United Kingdom; NIHR Great Ormond Street Hospital Biomedical Research Centre, London, United Kingdom.

    Source

    Seminars in pediatric neurology 29: 2019 Apr pg 71-82

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    31060727

    Citation

    Jungbluth, Heinz, and Francesco Muntoni. "Therapeutic Aspects in Congenital Myopathies." Seminars in Pediatric Neurology, vol. 29, 2019, pp. 71-82.
    Jungbluth H, Muntoni F. Therapeutic Aspects in Congenital Myopathies. Semin Pediatr Neurol. 2019;29:71-82.
    Jungbluth, H., & Muntoni, F. (2019). Therapeutic Aspects in Congenital Myopathies. Seminars in Pediatric Neurology, 29, pp. 71-82. doi:10.1016/j.spen.2019.01.004.
    Jungbluth H, Muntoni F. Therapeutic Aspects in Congenital Myopathies. Semin Pediatr Neurol. 2019;29:71-82. PubMed PMID: 31060727.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Therapeutic Aspects in Congenital Myopathies. AU - Jungbluth,Heinz, AU - Muntoni,Francesco, Y1 - 2019/01/16/ PY - 2019/5/8/entrez SP - 71 EP - 82 JF - Seminars in pediatric neurology JO - Semin Pediatr Neurol VL - 29 N2 - The congenital myopathies are a genetically heterogeneous and diverse group of early-onset, nondystrophic neuromuscular disorders. While the originally reported "classical" entities within this group - Central Core Disease, Multiminicore Disease, Nemaline Myopathy, and Centronuclear Myopathy - were defined by the predominant finding on muscle biopsy, "novel" forms with multiple, subtle, and unusual histopathologic features have been described more recently, reflective of an expanding phenotypical spectrum. The main disease mechanisms concern excitation-contraction coupling, intracellular calcium homeostasis, and thin/thick filament interactions. Management to date has been mainly supportive. Therapeutic strategies currently at various stages of exploration include genetic interventions aimed at direct correction of the underlying genetic defect, enzyme replacement therapy, and pharmacologic approaches, either specifically targeting the principal effect of the underlying gene mutation, or addressing its downstream consequences more generally. Clinical trial development is accelerating but will require more robust natural history data and tailored outcome measures. SN - 1558-0776 UR - https://www.unboundmedicine.com/medline/citation/31060727/Therapeutic_Aspects_in_Congenital_Myopathies L2 - https://linkinghub.elsevier.com/retrieve/pii/S1071-9091(19)30004-X DB - PRIME DP - Unbound Medicine ER -