Tetrahydrobiopterin as a novel therapeutic intervention for autism.

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.