{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T23:36:10Z","timestamp":1770420970253,"version":"3.49.0"},"reference-count":37,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,12,22]],"date-time":"2023-12-22T00:00:00Z","timestamp":1703203200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016065","name":"Stichting Stofwisselkracht","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mevalonate kinase deficiency (MKD) is an autoinflammatory metabolic disorder caused by bi\u2010allelic loss\u2010of\u2010function variants in the <jats:italic>MVK<\/jats:italic> gene, resulting in decreased activity of the encoded mevalonate kinase (MK). Clinical presentation ranges from the severe early\u2010lethal mevalonic aciduria to the milder hyper\u2010IgD syndrome (MKD\u2013HIDS), and is in the majority of patients associated with recurrent inflammatory episodes with often unclear cause. Previous studies with MKD\u2013HIDS patient cells indicated that increased temperature, as caused by fever during an inflammatory episode, lowers the residual MK activity, which causes a temporary shortage of non\u2010sterol isoprenoids that promotes the further development of inflammation. Because an increase of the residual MK activity is expected to make MKD\u2013HIDS patients less sensitive to developing inflammatory episodes, we established a cell\u2010based screen that can be used to identify compounds and\/or therapeutic targets that promote this increase. Using a reporter HeLa cell line that stably expresses the most common MKD\u2013HIDS variant, MK\u2010V377I, C\u2010terminally tagged with bioluminescent NanoLuc luciferase (nLuc), we screened the Prestwick Chemical Library\u00ae, which includes 1280 FDA\u2010approved compounds. Multiple compounds increased MK\u2010V377I\u2010nLuc bioluminescence, including steroids (i.e., glucocorticoids, estrogens, and progestogens), statins and antineoplastic drugs. The glucocorticoids increased MK\u2010V377I\u2010nLuc bioluminescence through glucocorticoid receptor signaling. Subsequent studies in MKD\u2013HIDS patient cells showed that the potent glucocorticoid clobetasol propionate increases gene transcription of <jats:italic>MVK<\/jats:italic> and other genes regulated by the transcription factor sterol regulatory element\u2010binding protein 2 (SREBP\u20102). Our results suggest that increasing the flux through the isoprenoid biosynthesis pathway by targeting the glucocorticoid receptor or SREBP\u20102 could be a potential therapeutic strategy in MKD\u2013HIDS.<\/jats:p>","DOI":"10.1002\/jimd.12698","type":"journal-article","created":{"date-parts":[[2023,12,22]],"date-time":"2023-12-22T10:39:53Z","timestamp":1703241593000},"page":"302-316","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Identification of <scp>FDA<\/scp>\u2010approved drugs that increase mevalonate kinase in hyper <scp>IgD<\/scp> syndrome"],"prefix":"10.1002","volume":"47","author":[{"given":"Frouwkje A.","family":"Politiek","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Laboratory Genetic Metabolic Diseases Amsterdam University Medical Centers, Academic Medical Center  Amsterdam the Netherlands"},{"name":"Amsterdam Gastroenterology Endocrinology Metabolism  Amsterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marjolein","family":"Turkenburg","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Laboratory Genetic Metabolic Diseases Amsterdam University Medical Centers, Academic Medical Center  Amsterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janet","family":"Koster","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Laboratory Genetic Metabolic Diseases Amsterdam University Medical Centers, Academic Medical Center  Amsterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rob","family":"Ofman","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Laboratory Genetic Metabolic Diseases Amsterdam University Medical Centers, Academic Medical Center  Amsterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5147-7106","authenticated-orcid":false,"given":"Hans R.","family":"Waterham","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Laboratory Genetic Metabolic Diseases Amsterdam University Medical Centers, Academic Medical Center  Amsterdam the Netherlands"},{"name":"Amsterdam Gastroenterology Endocrinology Metabolism  Amsterdam the Netherlands"},{"name":"Amsterdam Reproduction &amp; 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