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A quick recap: BH4 is a hold-my-hand cofactor involved in some pretty important biochemical reactions; notably quite a few utilising those interesting aromatic amino acids (see here) and their neurotransmitter relations. Deficiency of BH4 has a few consequences as one might imagine; one of the important ones being a build up of the amino acid phenylalanine, which as seen in PKU and perhaps other conditions, is not necessarily a great position to be in.
Going back to the autism connection, the paper by Cheryl Klaiman and colleagues* caught my eye, as they reported on the results of a gold-standard double-blind, placebo-controlled trial of BH4 in young children (3-7 years old) diagnosed with an autism spectrum disorder (ASD). Actually, you can see a little bit more about their trial from their entry in the ClinicalTrials.gov database (see here) with the requirement for the study authors to update their study details!! (as of July 2013).
Anyhow, in their fairly small participant group they looked at children taking BH4 - 20mg/Kg body weight per day - compared with those taking a placebo for 16 weeks and examined various autism and related behaviours. They reported no statistically significant difference on their primary outcome measure (the CGI-I and CGI-S) but..... there were a number of significant improvements noted on some of the secondary measures used including behaviours related to social awareness, hyperactivity and aspects of language. Importantly too, reported side-effects from BH4 were minimal and on a par with those reported by the placebo group. They conclude: "These results indicate that BH4 offers promise in reducing symptoms of ASD".
These are interesting results both insofar as what is reported and the speculations about what BH4 might be doing. Unfortunately, this study did not report on any specific biochemical measures so it's slightly difficult to add anything further even though just some simple measures of things like blood phenylalanine levels** or even nitric oxide (NO) metabolites*** would, I dare say, have been quite revealing.
I'm not going quibble however about this paper because it adds to the already interesting evidence base on BH4 for at least some cases of autism. That and the quite impressive record on few and far between side-effects of BH4 makes for another interesting potential therapeutic agent (and its targets) should anyone wish to take up the research gauntlet further.
* Klaiman C. et al. Tetrahydrobiopterin as a treatment for autism spectrum disorders: a double-blind, placebo-controlled trial. J Child Adolesc Psychopharmacol. 2013 Jun;23(5):320-8. doi: 10.1089/cap.2012.0127.
** Burton BK. et al. Sapropterin therapy increases stability of blood phenylalanine levels in patients with BH4-responsive phenylketonuria (PKU). Mol Genet Metab. 2010 Oct-Nov;101(2-3):110-4. doi: 10.1016/j.ymgme.2010.06.015.
*** Frye RE. et al. Metabolic effects of sapropterin treatment in autism spectrum disorder: a preliminary study. Transl Psychiatry. 2013 Mar 5;3:e237. doi: 10.1038/tp.2013.14.
Klaiman C, Huffman L, Masaki L, & Elliott GR (2013). Tetrahydrobiopterin as a treatment for autism spectrum disorders: a double-blind, placebo-controlled trial. Journal of child and adolescent psychopharmacology, 23 (5), 320-8 PMID: 23782126