肾上腺脑白质营养不良最新治疗研究进展  

Advances in the treatment of adrenoleukodystrophy

作　　者：刘晓黎 曹立 LIU Xiaoli;CAO Li(Department of Neurology,Fengxian District Central Hospital Affiliated to Shanghai University of Medicine&Health Sciences,Shanghai 201406,China;Department of Neurology,Shanghai Sixth People′s Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200233,China;Shanghai Neurological Rare Disease Biobank and Precision Diagnostic Technical Service Platform,Shanghai 200233,China)

机构地区：[1]上海健康医学院附属奉贤区中心医院神经内科,上海201406 [2]上海交通大学医学院附属第六人民医院神经内科,上海200233 [3]上海市神经系统罕见疾病生物样本库和精准诊断专业技术服务平台(筹),上海200233

出　　处：《上海交通大学学报(医学版)》2025年第1期95-100,共6页Journal of Shanghai Jiao tong University:Medical Science

基　　金：国家自然科学基金(82371255);上海科技创新行动计划(23DZ2291500);上海市卫生健康委员会项目(2022LJ011);奉贤区科学技术委员会项目(20231207);上海市第六人民医院医疗集团科研基金计划项目;上海健康医学院2023年师资人才百人库项目。

摘　　要：肾上腺脑白质营养不良(adrenoleukodystrophy,ALD)是一种呈X连锁的、潜在致命的过氧化物酶体疾病,其主要临床表型是肾上腺脊髓神经病(adrenomyeloneuropathy,AMN)、脑型肾上腺脑白质营养不良(cerebral adrenoleukodystrophy,CALD)和原发性肾上腺功能不全(primary adrenal insufficiency)。ALD的临床表型不可预测,没有基因型-表型相关性,也不能根据血浆中极长链脂肪酸(very long chain fatty acid,VLCFA)水平预测疾病病程,并且表型之间可以有很大的差异。目前尚无法彻底治愈该疾病,针对具体的表型有不同的治疗选择。AMN只能进行支持性治疗,但早期CALD可以通过异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,allo-HSCT)和转基因自体造血干细胞移植(transgenic autologous hematopoietic stem cell transplantation,trans-ASCT)来稳定病情,原发性肾上腺功能不全可以通过激素替代疗法来治疗。allo-HSCT和trans-ASCT可以阻止早期CALD的进展,但不能逆转AMN的变化或阻止肾上腺功能不全的进程,也不能阻止晚期CALD患者神经功能障碍和死亡。近年来,多项针对ALD的药物临床试验披露了对ALD有治疗价值的结果。trans-ASCT和基因编辑治疗在动物模型和临床试验中亦有所突破,为不能行allo-HSCT治疗的ALD患者提供了替代选择。该文综述了ALD最新治疗研究成果,以期为临床提供借鉴。Adrenoleukodystrophy(ALD)is an X-linked,potentially fatal peroxisome disease,characterized by three main clinical phenotypes:adrenomyeloneuropathy(AMN),cerebral adrenoleukodystrophy(CALD),and primary adrenal insufficiency.The clinical phenotypes of ALD are unpredictable,with no genotype-phenotype correlation,and disease progression cannot be predicted based on very long chain fatty acid(VLCFA)levels in plasma.Additionally,the phenotypes can exhibit significant variability.Currently,no definitive treatment for this disease exists,and treatment options vary depending on the specific phenotypes.For AMN,only symptomatic supportive treatment is available.However,early CALD can be stabilized through allogeneic hematopoietic stem cell transplantation(allo-HSCT)and transgenic autologous hematopoietic stem cell transplantation(transASCT),and primary adrenal insufficiency can be treated through hormone replacement therapy.Allo-HSCT and trans-ASCT can prevent the progression of early CALD,but cannot reverse the changes of AMN or halt the progression of adrenal insufficiency.Furthermore,they cannot prevent neurological dysfunction or death in terminal CALD.In recent years,multiple clinical trials of drugs targeting ALD have demonstrated therapeutic potential for ALD.Trans-ASCT and gene editing therapy have also made breakthroughs in animal models and clinical trials,providing alternative options for ALD patients ineligible for allo-HSCT treatment.This paper reviews the latest therapeutic research results of ALD and provides a basis for clinical practice.

关 键 词：肾上腺脑白质营养不良 脑型肾上腺脑白质营养不良 肾上腺脊髓神经病 原发性肾上腺功能不全 造血干细胞移植 

分 类 号：R742.8[医药卫生—神经病学与精神病学] R744.9[医药卫生—临床医学] R586.1R741.05