Extracellular mitochondrial ATP, suramin, and autism?

& 2013 Elsevier HS Journals, Inc. All rights reserved. A recent publication reported that pregnant mice injected with the viral-like material Poly(I:C) produced, as previously known, offspring that exhibit behavior reminiscent of autism; it also reported that therapy with the antipurinergic drug suramin, used to treat the African disease trypanosomiasis, blocked ATP (a purine)-dependent biochemical and behavioral changes in these mice. The authors asserted that this represents a new theory of mitochondrial-derived purinergic chemicals leaking outside a cell and signaling danger to surrounding cells. This is an exciting finding and may suggest an important role of extracellular ATP in autism. However, this theory is apparently contrary to numerous reports of dysfunctional mitochondria and reduced ATP in patients with autism. The release of mitochondrial molecules extracellularly is not new. Extracellular ATP was previously considered a universal alarm signal released from cells under stress and capable of affecting neighboring cells, including mast cells. Extracellular ATP was also reported to augment inflammatory brain disease, microglial survival, as well as trigger and maintain inflammation in asthmatic airways. Nevertheless the findings by Naviaux et al, are supported by previous studies showing that extracellular mitochondrial material could be released from activated mast cells, unique immune cells involved in allergies and eczema. Many patients with autism have food allergies and allergic-like symptoms suggesting mast cell activation. A recent epidemiologic study of 92,642 children reported a strong correlation between atopic dermatitis (ie, eczema), attention deficit hyperactivity disorder, and autism. Moreover, children with mastocytosis, a spectrum of diseases that present with skin allergies,