The effect of intrathecal recombinant arylsulfatase A therapy on structural brain magnetic resonance imaging in children with metachromatic leukodystrophy

IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Samuel Groeschel, Shanice Beerepoot, Lucas Bastian Amedick, Ingeborg Krӓgeloh-Mann, Jing Li, David A. H. Whiteman, Nicole I. Wolf, John D. Port
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Abstract

This study aimed to evaluate the effect of intrathecal (IT) recombinant human arylsulfatase A (rhASA) on magnetic resonance imaging (MRI)-assessed brain tissue changes in children with metachromatic leukodystrophy (MLD). In total, 510 MRI scans were collected from 12 intravenous (IV) rhASA-treated children with MLD, 24 IT rhASA-treated children with MLD, 32 children with untreated MLD, and 156 normally developing children. Linear mixed models were fitted to analyze the time courses of gray matter (GM) volume and fractional anisotropy (FA) in the posterior limb of the internal capsule. Time courses for demyelination load and FA in the centrum semiovale were visualized using locally estimated scatterplot smoothing regression curves. All assessed imaging parameters demonstrated structural evidence of neurological deterioration in children with MLD. GM volume was significantly lower at follow-up (median duration, 104 weeks) in IV rhASA-treated versus IT rhASA-treated children. GM volume decline over time was steeper in children receiving low-dose (10 or 30 mg) versus high-dose (100 mg) IT rhASA. Similar effects were observed for demyelination. FA in the posterior limb of the internal capsule showed a higher trend over time in IT rhASA-treated versus children with untreated MLD, but FA parameters were not different between children receiving the low doses versus those receiving the high dose. GM volume in IT rhASA-treated children showed a strong positive correlation with 88-item Gross Motor Function Measure score over time. In some children with MLD, IT administration of high-dose rhASA may delay neurological deterioration (assessed using MRI), offering potential therapeutic benefit.

Abstract Image

鞘内重组丙烯基硫酸酯酶 A 疗法对变色性白质营养不良症患儿脑结构磁共振成像的影响。
本研究旨在评估鞘内重组人丙烯基硫酸酯酶A(rhASA)对变色性白营养不良症(MLD)患儿磁共振成像(MRI)评估的脑组织变化的影响。研究人员共收集了12名经静脉注射(IV)rhASA治疗的变色性白质营养不良症患儿、24名经IT rhASA治疗的变色性白质营养不良症患儿、32名未经治疗的变色性白质营养不良症患儿和156名发育正常的患儿的510张磁共振成像扫描图像。线性混合模型用于分析内囊后缘灰质(GM)体积和分数各向异性(FA)的时间进程。利用局部估计的散点图平滑回归曲线,对半脱髓鞘中心的脱髓鞘负荷和FA的时间进程进行了可视化分析。所有评估的成像参数都显示,MLD患儿的神经系统结构有恶化的迹象。在随访期间(中位持续时间为104周),IV rhASA治疗的患儿与IT rhASA治疗的患儿相比,GM体积明显减少。接受低剂量(10或30毫克)与高剂量(100毫克)IT rhASA治疗的儿童的GM体积随时间的推移下降更快。在脱髓鞘方面也观察到类似的效果。内囊后缘的FA随时间推移呈上升趋势,接受IT rhASA治疗的患儿高于未接受治疗的MLD患儿,但FA参数在接受低剂量治疗的患儿与接受高剂量治疗的患儿之间没有差异。随着时间的推移,IT rhASA治疗儿童的GM体积与88项粗大运动功能测量评分呈强正相关。对于一些患有MLD的儿童,IT给药的高剂量rhASA可能会延缓神经系统的恶化(用核磁共振成像评估),从而提供潜在的治疗益处。
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来源期刊
Journal of Inherited Metabolic Disease
Journal of Inherited Metabolic Disease 医学-内分泌学与代谢
CiteScore
9.50
自引率
7.10%
发文量
117
审稿时长
4-8 weeks
期刊介绍: The Journal of Inherited Metabolic Disease (JIMD) is the official journal of the Society for the Study of Inborn Errors of Metabolism (SSIEM). By enhancing communication between workers in the field throughout the world, the JIMD aims to improve the management and understanding of inherited metabolic disorders. It publishes results of original research and new or important observations pertaining to any aspect of inherited metabolic disease in humans and higher animals. This includes clinical (medical, dental and veterinary), biochemical, genetic (including cytogenetic, molecular and population genetic), experimental (including cell biological), methodological, theoretical, epidemiological, ethical and counselling aspects. The JIMD also reviews important new developments or controversial issues relating to metabolic disorders and publishes reviews and short reports arising from the Society''s annual symposia. A distinction is made between peer-reviewed scientific material that is selected because of its significance for other professionals in the field and non-peer- reviewed material that aims to be important, controversial, interesting or entertaining (“Extras”).
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