Wright Melissa A, Demmitt-Rice Courtney, Van Haren Keith P, Lund Troy C, Eichler Florian, Bonkowsky Joshua L
Division of Pediatric Neurology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT, USA.
Department of Neurobiology, University of Utah School of Medicine, Salt Lake City, UT, USA.
J Child Neurol. 2025 Jul 23:8830738251353034. doi: 10.1177/08830738251353034.
ObjectivesMore than half of males with X-linked adrenoleukodystrophy (ALD) develop progressive, inflammatory cerebral demyelination (cerebral adrenoleukodystrophy). Treatment for cerebral adrenoleukodystrophy is limited with no standard therapies for advanced cerebral adrenoleukodystrophy. We reviewed cerebral adrenoleukodystrophy literature and expert opinion, compiling immunopathology, biomarkers, and therapies tested.MethodsWe reviewed published literature from January 1, 1970, through November 1, 2024, and surveyed expert clinicians worldwide caring for cerebral adrenoleukodystrophy patients for unpublished agent use.ResultsWe identified 20 publications with primary data on human cerebral adrenoleukodystrophy immunopathology. Seventeen publications reported cerebral adrenoleukodystrophy biomarkers. We identified 14 publications reporting use of 7 different agents; unpublished clinician reports identified use of 9 different agents.ConclusionsCerebral adrenoleukodystrophy immunopathology represents complex dysregulation of cytokines, macrophages, T cells, astrocytes, oligodendrocytes, and microglia. Partial responses to cerebral adrenoleukodystrophy were noted with intravenous immunoglobulin, sirolimus, leriglitazone, and mycophenolate. Our findings suggest consideration for a randomized platform trial of immunomodulatory agents for advanced cerebral adrenoleukodystrophy.
超过半数的X连锁肾上腺脑白质营养不良（ALD）男性患者会出现进行性炎症性脑脱髓鞘病变（脑型肾上腺脑白质营养不良）。脑型肾上腺脑白质营养不良的治疗方法有限，对于晚期脑型肾上腺脑白质营养不良尚无标准疗法。我们回顾了脑型肾上腺脑白质营养不良的文献及专家意见，汇总了免疫病理学、生物标志物及已测试的治疗方法。
我们回顾了1970年1月1日至2024年11月1日发表的文献，并调查了全球照料脑型肾上腺脑白质营养不良患者的专家临床医生关于未发表药物使用情况。
我们确定了20篇关于人脑型肾上腺脑白质营养不良免疫病理学的原始数据的出版物。17篇出版物报告了脑型肾上腺脑白质营养不良的生物标志物。我们确定了14篇报告使用7种不同药物的出版物；未发表的临床医生报告确定了9种不同药物的使用情况。
脑型肾上腺脑白质营养不良的免疫病理学表现为细胞因子、巨噬细胞、T细胞、星形胶质细胞、少突胶质细胞和小胶质细胞的复杂失调。静脉注射免疫球蛋白、西罗莫司、吡格列酮和霉酚酸酯对脑型肾上腺脑白质营养不良有部分疗效。我们的研究结果建议考虑对晚期脑型肾上腺脑白质营养不良进行免疫调节药物的随机平台试验。
