Effect of pioglitazone treatment on behavioral symptoms in autistic children
Effect of pioglitazone treatment on behavioral symptoms in autistic children
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DOI：
10.1186/1742-2094-4-3
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发表时间：
2007-01-05
影响因子：
9.3
通讯作者：
Feinstein, Douglas L.
中科院分区：
文献类型：
--
作者：
Boris, Marvin;Kaiser, Claudia C.;Feinstein, Douglas L.
简介：自闭症是一种复杂的神经发育障碍，其在患者中具有症状诊断，其特征在于语言/交流，行为和社会互动障碍。自闭症的确切原因在很大程度上是未知的，但据推测，免疫和炎症反应，特别是那些Th 2型，可能涉及。噻唑烷二酮（TZD）是过氧化物酶体增殖物激活受体γ（PPAR γ）的激动剂，过氧化物酶体增殖物激活受体γ是调节胰岛素敏感性的核激素受体，并且已经显示在活化的T淋巴细胞中诱导凋亡并在神经胶质细胞中发挥抗炎作用。TZD吡格列酮（Actos）是FDA批准的用于治疗2型糖尿病的PPAR γ激动剂，具有良好的安全性，目前正在其他神经系统疾病（包括AD和MS）的临床试验中进行测试。因此，我们在一小群诊断为自闭症的儿童中测试了口服吡格列酮的安全性和治疗潜力。病例描述：向父母解释服用吡格列酮的原理和风险，获得知情同意，并以30或60 mg/天p.o.开始治疗。共招募了25名儿童（平均年龄7.9 ± 0.7岁）。通过测量代谢谱和血压来评估安全性;通过异常行为检查表（ABC）来评估对行为症状的影响，异常行为检查表（ABC）测量在基线和治疗3-4个月后进行的多动、不适当的言语、易怒、嗜睡和刻板。吡格列酮3-4个月诱导明显的临床改善，无不良事件。未观察到不良反应，行为测量显示5个亚类中有4个显著降低（易怒、嗜睡、刻板和多动）。改善行为与患者年龄呈负相关，表明对年轻patients.Conclusion：吡格列酮应考虑进一步测试自闭症患者的治疗潜力。
Introduction: Autism is complex neuro-developmental disorder which has a symptomatic diagnosis in patients characterized by disorders in language/communication, behavior, and social interactions. The exact causes for autism are largely unknown, but is has been speculated that immune and inflammatory responses, particularly those of Th2 type, may be involved. Thiazolidinediones (TZDs) are agonists of the peroxisome proliferator activated receptor gamma ( PPAR gamma), a nuclear hormone receptor which modulates insulin sensitivity, and have been shown to induce apoptosis in activated T-lymphocytes and exert anti-inflammatory effects in glial cells. The TZD pioglitazone ( Actos) is an FDA-approved PPAR gamma agonist used to treat type 2 diabetes, with a good safety profile, currently being tested in clinical trials of other neurological diseases including AD and MS. We therefore tested the safety and therapeutic potential of oral pioglitazone in a small cohort of children with diagnosed autism.Case description: The rationale and risks of taking pioglitazone were explained to the parents, consent was obtained, and treatment was initiated at either 30 or 60 mg per day p.o. A total of 25 children ( average age 7.9 +/- 0.7 year old) were enrolled. Safety was assessed by measurements of metabolic profiles and blood pressure; effects on behavioral symptoms were assessed by the Aberrant Behavior Checklist (ABC), which measures hyperactivity, inappropriate speech, irritability, lethargy, and stereotypy, done at baseline and after 3-4 months of treatment.Discussion and evaluation: In a small cohort of autistic children, daily treatment with 30 or 60 mg p.o. pioglitazone for 3-4 months induced apparent clinical improvement without adverse events. There were no adverse effects noted and behavioral measurements revealed a significant decrease in 4 out of 5 subcategories ( irritability, lethargy, stereotypy, and hyperactivity). Improved behaviors were inversely correlated with patient age, indicating stronger effects on the younger patients.Conclusion: Pioglitazone should be considered for further testing of therapeutic potential in autistic patients.