亨廷顿病给予肌酸补充物降低大脑的谷氨酸水平
Creatine supplementation lowers brain glutamate levels in Huntington’ s disease作者机构：Department of Neurology Klinikum Grosshadern University of Munich Marchioninistr. 15 81377 Munich Germany Dr.
出 版 物：《世界核心医学期刊文摘（神经病学分册）》 (Digest of the World Core Medical Journals:Clinical Neurology)
年 卷 期：2005年第1卷第6期
页 面：34-35页
学科分类：1002[医学-临床医学] 100204[医学-神经病学] 10[医学]
主 题：亨廷顿病 肌酸 症状持续时间 神经退行性病变 兴奋毒性 临床试验 保护效应 临床终点 磁共振波谱成像 乳酸盐
摘 要：There is evidence from in vitro and animal experiments that oral creatine (Cr) supplementation might prevent or slow down neurodegeneration in Huntington’ s disease (HD). However, this neuroprotective effect could not be replicated in clinical trials, possibly owing to treatment periods being too short to impact on clinical endpoints. We used proton magnetic resonance spectroscopy (1H- MRS) as a surrogate marker to evaluate the effect of Cr supplementation on brain metabolite levels in HD. Twenty patients (age 46 ± 7.3 years, mean duration of symptoms 4.0 ± 2.1 years, number of CAG repeats 44.5 ± 2.7) were included. The primary endpoint was metabolic alteration as measured by 1H- MRS in the parieto- occipital cortex before (t1) and after 8- 10 weeks (t2) of Cr administration. Secondary measures comprised the motor section of the Unified Huntington’ s Disease Rating Scale and the Mini Mental State Examination. 1H- MRS showed a 15.6% decrease of unresolved glutamate (Glu) + glutamine (Gln; Glu + Gln = Glx; p 0.001) and a 7.8 % decrease of Glu (p 0.027) after Cr treatment. N- acetylaspartate trended to fall (p = 0.073) whereas total Cr, choline- containing compounds, glucose, and lactate remained unchanged. There was no effect on clinical rating scales. This cortical Glx and Glu decrease may be explained by Cr enhancing the energy- dependent conversion of Glu to Gln via the Glu- Gln cycle, a pathway known to be impaired in HD. Since Glu- mediated excitotoxicity is presumably pivotal in HD pathogenesis, these results indicate a therapeutic potential of Cr in HD. Thus, long- term clinical trials are warranted.
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