GLYCEROL-TRIERUCATE THERAPY OF ADRENOLEUKODYSTROPHY

X连锁肾上腺脑白质营养不良(ALD)的关键生化异常是 饱和超长链脂肪酸(VLCFA)在体内的积累 组织和体液，由于一种过氧化物酶的遗传缺陷 通常会降解这些物质。ALD主要影响肾上腺 皮质、神经系统白质和睾丸。而内分泌 缺陷可以通过类固醇替代来帮助，这是一种神经功能障碍 无法治疗，往往会导致严重残疾和过早死亡。 神经受累范围从Mean的快速脑脱髓鞘 发病年龄为7.2±1.7岁(SD)，进展较慢 成人脊髓和周围神经受累 (肾上腺髓神经病)。我们实验室开展了一项全国性的研究项目 X-连锁ALD和过氧化物酶体疾病的诊断，并通过 该项目已经确认了700多名患有X-连锁ALD的男性，到目前为止 在任何地方都有最大的这种疾病患者群体。 最近的研究表明，一种新的饮食方法可以使 2~4岁ALD患者血浆中饱和VLCFA水平的变化 几周。该疗法包括口服甘油。 三芥酸(GTE)油和某些其他饮食修改。 ALD的诊断可以在出生后早期(以及 产前)，至少在神经性疾病发作前几年 未经治疗的患者的残疾。细菌的显著生化效应 新的养生法首次提供了测试早期 饱和VLCFA正常化可预防或改善神经功能障碍 阿尔茨海默病的残疾。拟议的研究包括三个部分：1)双重- 成年肾上腺髓质神经病患者的盲法试验 神经受累的ALD杂合子；2)一项预防试验 有ALD生化缺陷的无神经症状男孩；3) 一项对有神经学症状的男孩的研究 这项研究将与100多名未接受治疗的儿童进行比较。 曾在我们实验室确诊的ALD患者。

The key biochemical abnormality in X-linked adrenoleukodystrophy (ALD) is the accumulation of saturated very long chain fatty acids (VLCFA) in tissues and body fluids, due to a genetic defect of a peroxisomal enzyme that normally degrades these substances. ALD affects mainly the adrenal cortex, nervous system white matter and testis. While the endocrine deficits can be helped by steroid replacement, the neurological disability cannot be treated and often leads to severe disability and premature death. Neurological involvement ranges from rapid cerebral demyelination with mean age of onset at age 7.2 + 1.7 (SD) years, to much more slowly progressive spinal cord and peripheral nerve involvement in adults (adrenomyeloneuropathy). Our laboratory conducts a national program for the diagnosis of X-linked ALD and peroxisomal disorders, and through this program has identified more than 700 males with X-linked ALD, by far the largest group of patients with this disorder anywhere. Recent studies have demonstrated that a new dietary approach can normalize the levels of saturated VLCFA in the plasma of patients with ALD within 2-4 weeks. The regimen involves the oral administration of a glycerol trierucate (GTE) oil together with certain other dietary modifications. Diagnosis ALD can be achieved in the early postnatal period (as well as prenatally), at least several years before the onset of neurological disability in untreated patients. The striking biochemical effect of the new regimen for the first time offers the opportunity to test whether early normalization of saturated VLCFA can prevent or ameliorate the neurological disability in ALD. The proposed study has three components: 1) a double- blinded trial involving adults with adrenomyeloneuropathy and neurologically involved ALD heterozygotes; 2) a prevention trial for neurologically asymptomatic boys with the biochemical defect of ALD; and 3) a study of neurologically symptomatic boys in whom the rate of neurological progression will be compared with that in more than 100 untreated childhood ALD patients who had previously been diagnosed in our laboratory.