Tetrahydrobiopterin as a novel therapeutic intervention for autism

Summary

Tetrahydrobiopterin (BH₄) 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 BH₄ is reported to be depressed in children with ASD. Over the past 25 years, several clinical trials have suggested that treatment with BH₄ improves ASD symptomatology in some individuals. Two ongoing clinical protocols may help further define the efficacy of BH₄ 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 BH₄. 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 BH₄ treatment in children with ASD is currently underway. Safety studies from the commercially available forms of BH₄ document the low incidence of AEs, particularly serious AEs. Studies have also documented the ability of BH₄ to cross the blood-brain barrier. Based on the importance of BH₄ in neurodevelopmental metabolic pathways, the safety of BH₄ treatment, and the evidence for a therapeutic benefit of BH₄ treatment in children with ASD, we conclude that BH₄ represents a novel therapy for ASD, one that may gain wider use after further clinical studies have established efficacy and treatment guidelines.