{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T07:52:58Z","timestamp":1791359578237,"version":"4.3.1"},"reference-count":29,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":279,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100005646","name":"Actelion Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005646","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004339","name":"Sanofi","doi-asserted-by":"publisher","award":["SGZ201912859"],"award-info":[{"award-number":["SGZ201912859"]}],"id":[{"id":"10.13039\/100004339","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioMed Research International"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Metachromatic leukodystrophy (MLD) is a rare metabolic disease characterized by demyelination and inherited in an autosomal recessive manner. It is caused by mutations in the arylsulfatase A (\n                      <jats:italic>ARSA<\/jats:italic>\n                      ) gene. When ARSA enzyme activity is lacking or reduced, sulfatides and lysosulfatides accumulate, particularly within the myelin sheath, resulting in various symptoms, including developmental delay and movement disorders. Gene therapy using hematopoietic stem cells has been developed and approved for MLD; however, the long\u2010term risks associated with lentiviral vectors remain uncertain. Therefore, expanding the available therapeutic options for patients with MLD remains essential.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study is aimed at exploring two potential drugs that may induce heat\u2010shock protein, along with 765 FDA\u2010approved drugs that might enhance ARSA enzyme activity, using four fibroblast cell lines derived from patients with MLD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Fibroblasts derived from patients with MLD exhibited low ARSA enzyme activities and increased sulfatide accumulation. Geranylgeranylacetone, an HSP70 inducer, increased the enzyme activity, while arimoclomol, an HSP coinducer, did not affect it. Furthermore, a screening test revealed that two of the 765 FDA\u2010approved drugs increased the enzyme activity in MLD fibroblasts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These results lay the groundwork for future research into the development of new therapeutic options for MLD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/bmri\/1945300","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T07:29:04Z","timestamp":1791358144000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["In Vitro Screening of an FDA\u2010Approved Chemical Library for Arylsulfatase A Using Fibroblast Cells Derived From Patients With MLD"],"prefix":"10.1155","volume":"2026","author":[{"given":"Takashi","family":"Miyajima","sequence":"first","affiliation":[{"name":"Advanced 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