A Functional Human Glycogen Debranching Enzyme Encoded by a Synthetic Gene: Its Implications for Glycogen Storage Disease Type III Management

Title:A Functional Human Glycogen Debranching Enzyme Encoded by a Synthetic Gene: Its Implications for Glycogen Storage Disease Type III Management

Volume: 31

Author(s): Doriana Triggiani*, Olivia C. Demurtas, Elena Illiano, Silvia Massa, Alessandra Pasquo, Carlo Dionisi-Vici, Carmela Marino, Giovanni Giuliano and Rosella Franconi

Affiliation:

• Department for Sustainability, ENEA, Italian National Agency for New Technologies, Energy and Sustainable Economic Development, Casaccia Research Center, Via Anguillarese 301, 00123, Rome, Italy
• AIG, Associazione Italiana Glicogenosi, ONLUS, Via Roma, 2/G 20090 Assago, Milan, Italy

Abstract: Background: Glycogen Storage Disease type III (GSD III) is a metabolic disorder resulting from a deficiency of the Glycogen Debranching Enzyme (GDE), a large monomeric protein (approximately 170 kDa) with cytoplasmic localization and two distinct enzymatic activities: 4-α-glucantransferase and amylo-α-1,6-glucosidase. Mutations in the Agl gene, with consequent deficiency in GDE, lead to the accumulation of abnormal/toxic glycogen with shorter chains (phosphorylase limit dextrin, PLD) in skeletal and/or heart muscle and/or in the liver. Currently, there is no targeted therapy, and available treatments are symptomatic, relying on specific diets.

Methods: Enzyme Replacement Therapy (ERT) might represent a potential therapeutic strategy for GSD III. Moreover, the single-gene nature of GSD III, the subcellular localization of GDE, and the type of affected tissues represent ideal conditions for exploring gene therapy approaches. Toward this direction, we designed a synthetic, codon-optimized cDNA encoding the human GDE.

Results: This gene yielded high amounts of soluble, enzymatically active protein in Escherichia coli. Moreover, when transfected in Human Embryonic Kidney cells (HEK-293), it successfully encoded a functional GDE.

Conclusion: These results suggest that our gene or protein might complement the missing function in GSD III patients, opening the door to further exploration of therapeutic approaches for this disease.

Cite this article as:

Triggiani Doriana*, Demurtas Olivia C., Illiano Elena, Massa Silvia, Pasquo Alessandra, Dionisi-Vici Carlo, Marino Carmela, Giuliano Giovanni and Franconi Rosella, A Functional Human Glycogen Debranching Enzyme Encoded by a Synthetic Gene: Its Implications for Glycogen Storage Disease Type III Management, Protein & Peptide Letters 2024; 31 () . https://dx.doi.org/10.2174/0109298665307430240628063339

DOI https://dx.doi.org/10.2174/0109298665307430240628063339	Print ISSN 0929-8665
Publisher Name Bentham Science Publisher	Online ISSN 1875-5305