Boris Marvin, Kaiser Claudia C, Goldblatt Allan, Elice Michael W, Edelson Stephen M, Adams James B, Feinstein Douglas L
Woodbury, New York 11797, USA.
J Neuroinflammation. 2007 Jan 5;4:3. doi: 10.1186/1742-2094-4-3.
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 (PPARgamma), 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 PPARgamma 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.
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.
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.
Pioglitazone should be considered for further testing of therapeutic potential in autistic patients.
自闭症是一种复杂的神经发育障碍，其对患者的症状性诊断特征为语言/沟通、行为和社交互动方面的紊乱。自闭症的确切病因在很大程度上尚不清楚，但据推测免疫和炎症反应，尤其是Th2型反应，可能与之有关。噻唑烷二酮类药物（TZDs）是过氧化物酶体增殖物激活受体γ（PPARγ）的激动剂，PPARγ是一种调节胰岛素敏感性的核激素受体，已显示其可诱导活化的T淋巴细胞凋亡，并在神经胶质细胞中发挥抗炎作用。TZD类药物吡格列酮（艾可拓）是一种经美国食品药品监督管理局（FDA）批准的用于治疗2型糖尿病的PPARγ激动剂，具有良好的安全性，目前正在包括阿尔茨海默病（AD）和多发性硬化症（MS）在内的其他神经系统疾病的临床试验中进行测试。因此，我们在一小群已确诊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。
向家长解释了服用吡格列酮的基本原理和风险，获得了家长的同意，并开始每天口服30或60毫克进行治疗。总共招募了25名儿童（平均年龄7.9±0.7岁）。通过测量代谢指标和血压来评估安全性；通过异常行为检查表（ABC）评估对行为症状的影响，该检查表测量多动、言语不当、易怒、嗜睡和刻板行为，在基线时以及治疗3至4个月后进行评估。
在一小群自闭症儿童中，每天口服30或60毫克吡格列酮治疗3至4个月可带来明显的临床改善且无不良事件。未观察到不良反应，行为测量显示5个亚类中的4个（易怒、嗜睡、刻板行为和多动）有显著下降。行为改善与患者年龄呈负相关，表明对较年轻患者的效果更强。
应考虑对吡格列酮在自闭症患者中的治疗潜力进行进一步测试。
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