Division of Child and Adolescent Neurology and The Children's Learning Institute, Department of Pediatrics, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.
Neurotherapeutics. 2010 Jul;7(3):241-9. doi: 10.1016/j.nurt.2010.05.004.
Tetrahydrobiopterin (BH(4)) is an essential cofactor for several critical metabolic pathways that have been reported to be abnormal in autism spectrum disorder (ASD). In addition, the cerebrospinal fluid concentration of BH(4) is reported to be depressed in children with ASD. Over the past 25 years, several clinical trials have suggested that treatment with BH(4) improves ASD symptomatology in some individuals. Two ongoing clinical protocols may help further define the efficacy of BH(4) treatment in children with ASD. First, children with ASD who had low concentrations of cerebrospinal fluid or urine pterins were treated in an open-label manner with 20 mg/kg per day of BH(4). The majority of children (63%) responded positively to treatment, with minimal adverse events (AEs). Second, a double-blind placebo-controlled study examining the efficacy of 20 mg/kg per day of BH(4) treatment in children with ASD is currently underway. Safety studies from the commercially available forms of BH(4) document the low incidence of AEs, particularly serious AEs. Studies have also documented the ability of BH(4) to cross the blood-brain barrier. Based on the importance of BH(4) in neurodevelopmental metabolic pathways, the safety of BH(4) treatment, and the evidence for a therapeutic benefit of BH(4) treatment in children with ASD, we conclude that BH(4) represents a novel therapy for ASD, one that may gain wider use after further clinical studies have established efficacy and treatment guidelines.
四氢生物蝶呤（BH4）是几种关键代谢途径的必需辅助因子，这些代谢途径已被报道在自闭症谱系障碍（ASD）中异常。此外，有报道称，ASD 儿童的脑脊液 BH4 浓度降低。在过去的 25 年中，几项临床试验表明，BH4 治疗可改善一些个体的 ASD 症状。目前正在进行两项临床试验方案，可能有助于进一步确定 BH4 治疗 ASD 儿童的疗效。首先，采用开放标签的方式，对脑脊液或尿液蝶呤浓度较低的 ASD 儿童，每天用 20mg/kg 的 BH4 进行治疗。大多数儿童（63%）对治疗有积极反应，不良反应（AE）最小。其次，目前正在进行一项双盲安慰剂对照研究，以评估 20mg/kg 每天的 BH4 治疗 ASD 儿童的疗效。从市售 BH4 形式的安全性研究中可知，不良反应（AE）的发生率较低，尤其是严重的 AE。研究还记录了 BH4 穿过血脑屏障的能力。基于 BH4 在神经发育代谢途径中的重要性、BH4 治疗的安全性，以及 BH4 治疗 ASD 儿童的治疗益处的证据，我们得出结论，BH4 是一种治疗 ASD 的新方法，在进一步的临床研究确定疗效和治疗指南后，可能会得到更广泛的应用。
