A pilot open-label trial of minocycline in patients with autism and regressive features.
A pilot open-label trial of minocycline in patients with autism and regressive features.
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DOI：
10.1186/1866-1955-5-9
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发表时间：
2013
影响因子：
4.9
通讯作者：
Swedo SE
中科院分区：
文献类型：
--
作者：
Pardo CA;Buckley A;Thurm A;Lee LC;Azhagiri A;Neville DM;Swedo SE
米诺环素是一种四环素衍生物，易于穿过血脑屏障，似乎对各种神经系统疾病中的神经炎症、小胶质细胞活化和神经保护具有有益作用。据报道，小胶质细胞激活和神经炎症都与自闭症有关。该研究旨在评估米诺环素治疗对患有自闭症和有发育倒退史的儿童的神经炎症标志物和自闭症行为学的影响。11名儿童参加了为期6个月的米诺环素（1.4 mg/kg）开放标签试验。10名儿童完成了试验。在米诺环素治疗前和治疗结束时收集行为指标，并获得脑脊液（CSF）、血清和血浆，并分析神经炎症标志物。临床改善微不足道。实验室检测显示CSF中脑源性神经营养因子（BDNF）（P = 0.042）和肝生长因子（HGF）（P = 0.028）的截短形式的表达谱发生显著变化。在血清中，截短的BDNF形式和α-2巨球蛋白（α-2 M）的比率也显著降低（P = 0.028），而成熟的BDNF/α-2 M的比率显示治疗后无差异。当比较这些蛋白质的治疗前后水平时，仅趋化因子CXCL 8（IL-8）在血清中有显著差异（P = 0.047），而在CSF或血清中未观察到趋化因子如CCL 2（MCP-1）或细胞因子如TNF-α、CD 40 L、IL-6、IFN-γ和IL-1β的显著变化。在血浆金属蛋白酶（米诺环素作用的假定靶点）的谱中未观察到显著的治疗前和治疗后变化。CSF和血液中BDNF、CSF中HGF和血清中CXCL 8（IL-8）的治疗前和治疗后概况的变化表明米诺环素可能通过调节神经营养生长因子的产生而在CNS中产生作用。然而，在这一小组儿童中，在服用米诺环素6个月期间或之后没有观察到临床改善。NCT00409747
Minocycline is a tetracycline derivative that readily crosses the blood brain barrier and appears to have beneficial effects on neuroinflammation, microglial activation and neuroprotection in a variety of neurological disorders. Both microglial activation and neuroinflammation have been reported to be associated with autism. The study was designed to evaluate the effects of minocycline treatment on markers of neuroinflammation and autism symptomatology in children with autism and a history of developmental regression. Eleven children were enrolled in an open-label trial of six months of minocycline (1.4 mg/kg). Ten children completed the trial. Behavioral measures were collected and cerebrospinal fluid (CSF), serum and plasma were obtained before and at the end of minocycline treatment and were analyzed for markers of neuroinflammation. Clinical improvements were negligible. The laboratory assays demonstrated significant changes in the expression profile of the truncated form of brain derived neurotrophic factor (BDNF) (P = 0.042) and hepatic growth factor (HGF) (P = 0.028) in CSF. In serum, the ratio of the truncated BDNF form and α-2 macroglobulin (α-2 M), was also significantly lower (P = 0.028) while the mature BDNF/α-2 M ratio revealed no difference following treatment. Only the chemokine CXCL8 (IL-8) was significantly different (P = 0.047) in serum while no significant changes were observed in CSF or serum in chemokines such as CCL2 (MCP-1) or cytokines such as TNF-α, CD40L, IL-6, IFN-γ and IL-1β when pre- and post-treatment levels of these proteins were compared. No significant pre- and post-treatment changes were seen in the profiles of plasma metalloproteinases, putative targets of the effects of minocycline. Changes in the pre- and post-treatment profiles of BDNF in CSF and blood, HGF in CSF and CXCL8 (IL-8) in serum, suggest that minocycline may have effects in the CNS by modulating the production of neurotrophic growth factors. However, in this small group of children, no clinical improvements were observed during or after the six months of minocycline administration. NCT00409747
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影响因子：
3.9
作者：
Lord, C;Risi, S;Rutter, M
通讯作者：
Rutter, M
DOI：
10.1097/00004850-200411000-00004
发表时间：
2004-11-01
影响因子：
2.6
作者：
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通讯作者：
Kapfhammer, HP
影响因子：
8.3
作者：
Hayakawa, Kazuhide;Mishima, Kenichi;Fujiwara, Michihiro
通讯作者：
Fujiwara, Michihiro
影响因子：
9.9
作者：
Gordon, PH;Moore, DH;Miller, RG
通讯作者：
Miller, RG
影响因子：
3.3
作者：
Hussein, Mohamed Hamed;Daoud, Ghada A.;Togari, Hajime
通讯作者：
Togari, Hajime