Pharmacological approaches for treating glycogen storage disorders involving polyglucosan body accumulation

Or Kakhlon*

*Corresponding author for this work

    Research output: Contribution to journalReview articlepeer-review


    Introduction: Glycogen storage disorders (GSDs) are mainly caused by over-accumulation of normal or malconstructed glycogen. A few GSDs, Adult Polyglucosan Body Disease (APBD), Andersen Disease, Tarui Disease and Lafora Disease are also associated with pathogenic inclusion bodies called polyglucosan bodies (PB) consisting of malconstructed glycogen (polyglucosan) in complex with several enzymes of glycogen metabolism. A treatment for GSDs is urgently required. This review examines the pharmacological avenue for curing PB-involving GSDs. Areas covered: I describe here the pros and cons of the structure-based drug development approach. This functional module-based approach can generate efficacious drugs, but with a large pleiotropic potential. Solutions based on modulations of affinity and specificity of putative drugs and on multi-targeting are then described. Next I discuss the targets of GSD pharmacological therapy: glycogen synthase (GYS), glycogen metabolizing enzymes and inclusion bodies. Finally, image-based high-throughput screening (HTS) is described as a methodological platform for PB-involving GSD drug discovery. Expert opinion: The conclusion of this review is that the pharmacological approach should be the leading therapeutic strategy for curing PB-involving GSDs. This approach enables broad characterization of underlying causes of PB-involving GSDs, an exhaustive examination of multiple mechanistic strategies for therapy and fast translational potential.

    Original languageAmerican English
    Pages (from-to)977-982
    Number of pages6
    JournalExpert Opinion on Orphan Drugs
    Issue number12
    StatePublished - 2 Dec 2017

    Bibliographical note

    Funding Information:
    Or Kakhlon has received support in the form of grants from Kamin (Israeli Ministry of Economics), Israel Ministry of Science and technology, APBD Research Foundation, and Association Francaise contre les Myopathies. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

    Publisher Copyright:
    © 2017 Informa UK Limited, trading as Taylor & Francis Group.


    • Glycogen storage disorders
    • glycogen
    • image-based high throughput screening
    • polyglucosan
    • polyglucosan bodies


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