{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T13:13:29Z","timestamp":1779196409935,"version":"3.51.4"},"reference-count":29,"publisher":"American Society for Clinical Investigation","issue":"17","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,9,6]]},"abstract":"<jats:p>\n                    Adult polyglucosan body disease (APBD) is a late-onset disease caused by intracellular accumulation of polyglucosan bodies, formed due to glycogen-branching enzyme (GBE) deficiency. To find a treatment for APBD, we screened 1,700 FDA-approved compounds in fibroblasts derived from APBD-modeling\n                    <jats:italic>GBE1<\/jats:italic>\n                    -knockin mice. Capitalizing on fluorescent periodic acid\u2013Schiff reagent, which interacts with polyglucosans in the cell, this screen discovered that the flavoring agent guaiacol can lower polyglucosans, a result also confirmed in APBD patient fibroblasts. Biochemical assays showed that guaiacol lowers basal and glucose 6-phosphate\u2013stimulated glycogen synthase (GYS) activity. Guaiacol also increased inactivating GYS1 phosphorylation and phosphorylation of the master activator of catabolism, AMP-dependent protein kinase. Guaiacol treatment in the APBD mouse model rescued grip strength and shorter lifespan. These treatments had no adverse effects except making the mice slightly hyperglycemic, possibly due to the reduced liver glycogen levels. In addition, treatment corrected penile prolapse in aged\n                    <jats:italic>GBE1<\/jats:italic>\n                    -knockin mice. Guaiacol\u2019s curative effects can be explained by its reduction of polyglucosans in peripheral nerve, liver, and heart, despite a short half-life of up to 60 minutes in most tissues. Our results form the basis to use guaiacol as a treatment and prepare for the clinical trials in APBD.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.99694","type":"journal-article","created":{"date-parts":[[2018,9,5]],"date-time":"2018-09-05T11:02:36Z","timestamp":1536145356000},"source":"Crossref","is-referenced-by-count":44,"title":["Guaiacol as a drug candidate for treating adult polyglucosan body disease"],"prefix":"10.1172","volume":"3","author":[{"given":"Or","family":"Kakhlon","sequence":"first","affiliation":[{"name":"Department of Neurology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Igor","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Structural Genomics Consortium, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonardo J.","family":"Solmesky","sequence":"additional","affiliation":[{"name":"Cell Screening Facility for Personalized Medicine, Department of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Netaly","family":"Khazanov","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Bar Ilan University, Ramat Gan, Israel."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Lossos","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael","family":"Alvarez","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Cell Biomedicine, Department of Biology, University of the Balearic Islands, Palma de Mallorca, Spain."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deniz","family":"Yetil","sequence":"additional","affiliation":[{"name":"Connecticut College, Newington, Connecticut USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergey","family":"Pampou","sequence":"additional","affiliation":[{"name":"Columbia University Department of Systems Biology Irving Cancer Research Center, New York, New York, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel","family":"Weil","sequence":"additional","affiliation":[{"name":"Cell Screening Facility for Personalized Medicine, Department of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel."},{"name":"Laboratory for Neurodegenerative Diseases and Personalized Medicine, Department of Cell Research and Immunology, The George S. 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