{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T10:54:04Z","timestamp":1792148044089,"version":"4.4.0"},"reference-count":33,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:00:00Z","timestamp":1792108800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:00:00Z","timestamp":1792108800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epileptic Disorders"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Lafora disease (LD) is a rare, fatal neurodegenerative epilepsy with no approved treatments. Empagliflozin, a sodium\u2010glucose cotransporter\u20102 (SGLT2) inhibitor, has shown neuroprotective actions in preclinical models through modulation of glycogen metabolism, induction of a pseudo\u2010ketogenic state, improved mitochondrial efficiency, and reduction of excitatory neurotransmission. Based on this rationale, we conducted a first\u2010in\u2010human pilot study of empagliflozin in two genetically confirmed LD patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Two patients with genetically confirmed LD received empagliflozin 10\u2009mg\/day for 6 months. Serial assessments included safety and tolerability, seizure frequency, myoclonus severity, electroencephalographic findings, neuropsychological and motor evaluations, brain MRI, and quantitative FDG\u2010PET with regional\n                      <jats:italic>Z<\/jats:italic>\n                      \u2010score analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Empagliflozin was safe and well tolerated, with no serious adverse events. Seizure frequency, myoclonus, and overall clinical status remained largely stable over 6 months, although some neuropsychological and motor measures showed variable changes between patients. EEG background activity and spike index were largely unchanged. Brain MRI showed stable mild cortical atrophy in both patients. In contrast, FDG\u2010PET revealed progressive and spatially expanding cerebral hypometabolism in both patients, with worsening regional\n                      <jats:italic>Z<\/jats:italic>\n                      \u2010scores, particularly in the parietal and precuneus regions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>In this first\u2010in\u2010human, 6\u2010month pilot study, empagliflozin showed acceptable short\u2010term safety and feasibility in LD, but no definitive conclusions on efficacy can be drawn. The dissociation between relative electroclinical stability and progressive metabolic impairment suggests that quantitative FDG\u2010PET may represent a sensitive biomarker for monitoring disease trajectory in this ultra\u2010rare epilepsy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epd2.70442","type":"journal-article","created":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T10:41:32Z","timestamp":1792147292000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Empagliflozin in Lafora disease: A first\u2010in\u2010human 6\u2010month pilot study with electroclinical and FDG\u2010PET findings"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3465-7540","authenticated-orcid":false,"given":"Giuseppe","family":"d'Orsi","sequence":"first","affiliation":[{"name":"Neurology Unit\u2014Epilepsy Center Fondazione IRCCS Casa Sollievo della Sofferenza  San Giovanni Rotondo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Liantonio","sequence":"additional","affiliation":[{"name":"Department of Pharmacy\u2014Drug Sciences University of Bari \u201cAldo Moro\u201d  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9140-5350","authenticated-orcid":false,"given":"Paola","family":"Imbrici","sequence":"additional","affiliation":[{"name":"Department of Pharmacy\u2014Drug Sciences University of Bari \u201cAldo Moro\u201d  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8536-5599","authenticated-orcid":false,"given":"Graziano","family":"Lolli","sequence":"additional","affiliation":[{"name":"Department of Cellular, Computational and Integrative Biology\u2013CIBio University of Trento  Trento Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia","family":"Dinoi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy\u2014Drug Sciences University of Bari \u201cAldo Moro\u201d  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8571-5125","authenticated-orcid":false,"given":"Elena","family":"Conte","sequence":"additional","affiliation":[{"name":"Department of Pharmacy\u2014Drug Sciences University of Bari \u201cAldo Moro\u201d  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5016-5805","authenticated-orcid":false,"given":"Cosimo Damiano","family":"Altomare","sequence":"additional","affiliation":[{"name":"Department of Pharmacy\u2014Drug Sciences University of Bari \u201cAldo Moro\u201d  Bari 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