{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T06:34:44Z","timestamp":1791441284385,"version":"4.3.3"},"reference-count":43,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,7,24]],"date-time":"2024-07-24T00:00:00Z","timestamp":1721779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007393","name":"Association Francaise contre les Myopathies","doi-asserted-by":"publisher","award":["23116"],"award-info":[{"award-number":["23116"]}],"id":[{"id":"10.13039\/100007393","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Yoran Institute of Genome Research","award":["23116"],"award-info":[{"award-number":["23116"]}]},{"name":"Personalized Medicine and by the Tel Aviv University Prajs-Drimmer Institute","award":["23116"],"award-info":[{"award-number":["23116"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Glycogen storage disease type III (GSDIII) is a hereditary glycogenosis caused by deficiency of the glycogen debranching enzyme (GDE), an enzyme, encoded by Agl, enabling glycogen degradation by catalyzing alpha-1,4-oligosaccharide side chain transfer and alpha-1,6-glucose cleavage. GDE deficiency causes accumulation of phosphorylase-limited dextrin, leading to liver disorder followed by fatal myopathy. Here, we tested the capacity of the new autophagosomal activator GHF-201 to alleviate disease burden by clearing pathogenic glycogen surcharge in the GSDIII mouse model Agl\u2212\/\u2212. We used open field, grip strength, and rotarod tests for evaluating GHF-201\u2019s effects on locomotion, a biochemistry panel to quantify hematological biomarkers, indirect calorimetry to quantify in vivo metabolism, transmission electron microscopy to quantify glycogen in muscle, and fibroblast image analysis to determine cellular features affected by GHF-201. GHF-201 was able to improve all locomotion parameters and partially reversed hypoglycemia, hyperlipidemia and liver and muscle malfunction in Agl\u2212\/\u2212 mice. Treated mice burnt carbohydrates more efficiently and showed significant improvement of aberrant ultrastructural muscle features. In GSDIII patient fibroblasts, GHF-201 restored mitochondrial membrane polarization and corrected lysosomal swelling. In conclusion, GHF-201 is a viable candidate for treating GSDIII as it recovered a wide range of its pathologies in vivo, in vitro, and ex vivo.<\/jats:p>","DOI":"10.3390\/biom14080893","type":"journal-article","created":{"date-parts":[[2024,7,24]],"date-time":"2024-07-24T15:47:32Z","timestamp":1721836052000},"page":"893","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Autophagic Activator GHF-201 Can Alleviate Pathology in a Mouse Model and in Patient Fibroblasts of Type III Glycogenosis"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7537-8070","authenticated-orcid":false,"given":"Kumudesh","family":"Mishra","sequence":"first","affiliation":[{"name":"Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah-Hebrew University Medical Center, Jerusalem 9112001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahar","family":"Sweetat","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah-Hebrew University Medical Center, Jerusalem 9112001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saja","family":"Baraghithy","sequence":"additional","affiliation":[{"name":"Obesity and Metabolism Laboratory, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0284-5448","authenticated-orcid":false,"given":"Uri","family":"Sprecher","sequence":"additional","affiliation":[{"name":"The Shmunis School of Biomedicine and Cancer Research, The George S. Wise Faculty for Life Sciences, Sagol School of Neurosciences, Tel Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monzer","family":"Marisat","sequence":"additional","affiliation":[{"name":"The Shmunis School of Biomedicine and Cancer Research, The George S. Wise Faculty for Life Sciences, Sagol School of Neurosciences, Tel Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sultan","family":"Bastu","sequence":"additional","affiliation":[{"name":"Centre de Reference de Maladies Neuromusculaires, UPEC\u2014Paris Est University, IMRB INSERM U955, Team Biology of the Neuromuscular System, Faculty of Medicine, APHP Hopital Henri Mondor, 1 Rue Gustave Eiffel, 94010 Creteil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hava","family":"Glickstein","sequence":"additional","affiliation":[{"name":"Electron Microscopy Unit, The Hebrew University-Hadassah Medical School, Ein Kerem, Jerusalem 9112001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0948-0093","authenticated-orcid":false,"given":"Joseph","family":"Tam","sequence":"additional","affiliation":[{"name":"Obesity and Metabolism Laboratory, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Rosenmann","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah-Hebrew University Medical Center, Jerusalem 9112001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5721-653X","authenticated-orcid":false,"given":"Miguel","family":"Weil","sequence":"additional","affiliation":[{"name":"The Shmunis School of Biomedicine and Cancer Research, The George S. Wise Faculty for Life Sciences, Sagol School of Neurosciences, Tel Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7871-8600","authenticated-orcid":false,"given":"Edoardo","family":"Malfatti","sequence":"additional","affiliation":[{"name":"Centre de Reference de Maladies Neuromusculaires, UPEC\u2014Paris Est University, IMRB INSERM U955, Team Biology of the Neuromuscular System, Faculty of Medicine, APHP Hopital Henri Mondor, 1 Rue Gustave Eiffel, 94010 Creteil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7435-6454","authenticated-orcid":false,"given":"Or","family":"Kakhlon","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah-Hebrew University Medical Center, Jerusalem 9112001, Israel"},{"name":"Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9112001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/S0021-9258(18)38501-6","article-title":"Structure of glycogens and amylopectins. 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