Trying to focus on a constellation

Naviaux et al have a paper out on "Antipurinergic Therapy Corrects the Autism-Like Features in the Poly(IC) Mouse Model", so naturally I was interested. One of the key points is in the introduction, which I reproduce below.

The majority of children with ASD develop disease as the result of interactions between large sets of genes and environmental factors. Common comorbidities in non-single-gene forms of ASD provide important clues to shared mechanisms of disease. Comorbidities include epilepsy [2], GI abnormalities [3], sleep disturbances [2], abnormalities in tryptophan metabolism and platelet hyperserotonemia [4], altered intracellular calcium and mitochondrial dynamics [5], hypoimmunoglobulinemia [6], hyperuricosuria [7], methylation disturbances [8], disturbances in sulfur [9] and glutathione metabolism [10], neuroinflammation [11], cerebellar vermis hypoplasia [12], and Purkinje cell loss [13]. We hypothesized that all of these clinical comorbidities can result from a single, evolutionarily conserved, metabolic state associated with a cellular danger response (CDR). Since mitochondria are located at the hub of the wheel of metabolism and play a central role in non-infectious cellular stress [14], innate immunity [15], inflammasome activation [16], and the stereotyped antiviral response [17], we searched for a signaling system that was both traceable to mitochondria and critical for innate immunity. Purinergic signaling via extracellular nucleotides like ATP and ADP satisfied these requirements. In the following study we tested the role of purinergic signaling in the maternal immune activation mouse model of ASD and show that antipurinergic therapy reverses the abnormalities found in this model.

I left the footnote references in as an aid to counting. That’s quite a constellation of problems, and it would be fascinating, and quite a coup for the authors, if they revolved around a common mechanism.

Their results seemed to show some improvement, but a larger study would be more convincing. One the brighter side, the intervention was at 6 weeks, which is roughly (4-8 weeks) when mice become sexually mature, which suggests that even fairly late intervention might be fruitful. If it all works, of course. We won’t know if this has any bearing on humans for a long time, nor whether this sort of thing addresses the whole constellation.

Still, something to keep an eye on.