{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:33:33Z","timestamp":1792787613721,"version":"4.5.0"},"reference-count":50,"publisher":"American Society for Clinical Investigation","issue":"18","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":42,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R01NS126193,R21NS131906,R33NS104384,R33NS106087,R01NS095884"],"award-info":[{"award-number":["R01NS126193,R21NS131906,R33NS104384,R33NS106087,R01NS095884"]}]},{"name":"ADLD Center","award":["ADLD-23-001-02"],"award-info":[{"award-number":["ADLD-23-001-02"]}]},{"name":"NIH\/NIA","award":["R01 AG083874,U24AG082930,P30 AG066468,RF1AG077474,R01 AG083156,R37 AG023651,R01 AG025516,R01 AG073267,R01 AG075336,R01 AG072641,P01 AG025204"],"award-info":[{"award-number":["R01 AG083874,U24AG082930,P30 AG066468,RF1AG077474,R01 AG083156,R37 AG023651,R01 AG025516,R01 AG073267,R01 AG075336,R01 AG072641,P01 AG025204"]}]},{"name":"NIH\/NINDS","award":["U01 NS131740,U01 NS141777"],"award-info":[{"award-number":["U01 NS131740,U01 NS141777"]}]},{"name":"NIH\/NIMH","award":["R01 MH108509"],"award-info":[{"award-number":["R01 MH108509"]}]},{"name":"Aging Mind Foundation","award":["DAF2255207"],"award-info":[{"award-number":["DAF2255207"]}]},{"name":"DoD","award":["HT94252320064"],"award-info":[{"award-number":["HT94252320064"]}]},{"name":"Anbridge Charitable Fund","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"Department of Psychiatry, University of Pittsburgh","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"https:\/\/ror.org\/01an3r305","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,22]]},"abstract":"<jats:p>\n                    Autosomal dominant leukodystrophy (ADLD) is a fatal adult-onset CNS demyelinating disorder for which no treatment exists. The majority of ADLD cases are caused by duplications of the lamin B1\n                    <jats:italic>(LMNB1<\/jats:italic>\n                    ) gene, resulting in increased LMNB1 expression. While reducing LMNB1 levels represents a logical therapeutic strategy, its efficacy has not been previously demonstrated in any in vivo model. Mouse models with oligodendrocyte-specific human LMNB1 (hLMNB1) overexpression recapitulate salient features of ADLD. Using a modified version of this model, where hLMNB1 can be inducibly downregulated, we demonstrated that hLMNB1 reduction can prevent or substantially ameliorate disease progression. Therapeutic effects were maximized when hLMNB1 reduction was induced before expected symptom onset, resulting in improvements in behavioral, biochemical, histopathological, and survival measures relative to those of untreated animals. Reducing hLMNB1 levels after symptom onset led to improved survival but mixed results for other disease phenotypes. In addition, we identified potential biomarkers that track disease progression. Furthermore, we demonstrated that near-complete knockdown of murine LMNB1 expression in adulthood did not result in any overt CNS phenotype. Together, these results provide a proof of concept supporting LMNB1 reduction as a therapeutic strategy and offer a rationale for treatments aimed at lowering levels of this protein in ADLD.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.207889","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T16:01:01Z","timestamp":1786464061000},"source":"Crossref","is-referenced-by-count":0,"title":["LMNB1 reduction is a potential therapeutic strategy in a mouse model of autosomal dominant leukodystrophy"],"prefix":"10.1172","volume":"11","author":[{"given":"Nathan","family":"Herdman","sequence":"first","affiliation":[{"name":"Department of Human Genetics, School of Public Health,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaveh","family":"Moradi","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, School of Public 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