Biomarkers in a Taurine Trial for Succinic Semialdehyde Dehydrogenase Deficiency
Biomarkers in a Taurine Trial for Succinic Semialdehyde Dehydrogenase Deficiency
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DOI：
10.1007/8904_2015_524
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发表时间：
2016-01-01
期刊：
影响因子：
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通讯作者：
Theodore, William H.
中科院分区：
文献类型：
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作者：
Schreiber, John M.;Pearl, Phillip L.;Theodore, William H.
目的：我们检验了以下假设：牛磺酸缺乏琥珀酸半醛脱氢酶（SSADH）的患者会降低皮质兴奋性（通过经颅磁刺激（TMS）测量）并改善认知，这是由于牛磺酸的部分GABA（A和B）受体激动剂作用以及在无效小鼠模型中从癫痫持续状态和过早致死中的拯救。方法：生物标志物，包括神经心理学测试，TMS，和CSF代谢产物进行了研究，在一个队列的患者和关闭三个月的牛磺酸treatment.Results：七名患者（5 M/2 F;年龄范围12-33岁）参加了这项开放标签的交叉研究。基线平均全量表智商（FSIQ）为44.1（范围34-55）。在6个月随访时返回的6名患者中，5名完成了治疗期间的认知测试（3 M/2F）;平均FSIQ = 43.4（范围33-51）。CSF生物标志物（n = 4例受试者）显示牛磺酸水平升高，但游离或总GABA无变化。经颅磁刺激（TMS）测量的基线皮质兴奋性与该人群先前的研究结果一致，皮质沉默期较短，缺乏长时间间隔的皮质内抑制。牛磺酸的患者表现出减少皮质沉默期和短间隔内抑制相比，他们关闭牛磺酸study.Interpretation：TMS表现出减少抑制牛磺酸的患者，在相反的研究假设，但符合其未能产生临床或认知改善。TMS可能是治疗小儿神经递质障碍的有用生物标志物。
Aim: We tested the hypothesis that patients with succinic semialdehyde dehydrogenase (SSADH) deficiency on taurine would have decreased cortical excitability as measured by transcranial magnetic stimulation (TMS) and improved cognition, due to taurine's partial GABA(A and B) receptor agonist effects and rescue in the null mouse model from status epilepticus and premature lethality.Method: Biomarkers including neuropsychological testing, TMS, and CSF metabolites were studied in a cohort of patients on and off three months' taurine treatment.Results: Seven patients (5M/2F; age range 12-33 years) were enrolled in this open-label crossover study. Baseline average full-scale IQ (FSIQ) was 44.1 (range 34-55). Of six who returned at 6-month follow-up, five completed cognitive testing (3M/2F) on therapy; average FSIQ = 43.4 (range 33-51). CSF biomarkers (n = 4 subjects) revealed elevation in taurine levels but no change in free or total GABA. Baseline cortical excitability measured with TMS agreed with previous findings in this population, with a short cortical silent period and lack of long-interval intra-cortical inhibition. Patients on taurine showed a decrease in cortical silent period and short-interval intracortical inhibition compared to their off taurine study.Interpretation: TMS demonstrated decreased inhibition in patients on taurine, in contrast to the study hypothesis, but consistent with its failure to produce clinical or cognitive improvement. TMS may be a useful biomarker for therapy in pediatric neurotransmitter disorders.