Key Point: Explanation of the nature of autistic brain cells leads to promising treatment.

Antipurinergic Therapy Corrects the Autism-Like Features in the Poly(IC) Mouse Model

Robert K. Naviaux, Zarazuela Zolkipli, Lin Wang, Tomohiro Nakayama, Jane C. Naviaux, Thuy P. Le, Michael A. Schuchbauer, Mihael Rogac, Qingbo Tang, Laura L. Dugan, Susan B. Powell. University of California San Diego School of Medicine, San Diego, California. PLoS ONE 8(3): e57380. doi:10.1371/journal.pone.0057380. March 2013.

Explanation notes from Ultrasound-Autism Connection:

Cells communicate cellular health and danger to neighboring cells via release of molecules called purinergic signaling. Danger signals cause brain cells to develop protections that interfere with communication between cells. The theory is that autism happens when cells get fastened in a defensive metabolic mode and fail to communicate together, which can interfere with brain function and development. If this is the case, it would explain how disparate environmental influences, for instance a pharmaceutical and a rise in body temperature, could produce the similar brain alterations. Acting on this theory, the researchers were able to reverse autistic symptoms in mice using a known inhibitor, suramin, most commonly used in treating sleeping sickness.


Autism spectrum disorders (ASDs) are caused by both genetic and environmental factors. Mitochondria act to connect genes and environment by regulating gene-encoded metabolic networks according to changes in the chemistry of the cell and its environment. Mitochondrial ATP and other metabolites are mitokines—signaling molecules made in mitochondria—that undergo regulated release from cells to communicate cellular health and danger to neighboring cells via purinergic signaling. The role of purinergic signaling has not yet been explored in autism spectrum disorders.

We found that antipurinergic therapy (APT) corrected 16 multisystem abnormalities that defined the ASD-like phenotype in this model. These included correction of the core social deficits and sensorimotor coordination abnormalities, prevention of cerebellar Purkinje cell loss, correction of the ultrastructural synaptic dysmorphology, and correction of the hypothermia, metabolic, mitochondrial, P2Y2 and P2X7 purinergic receptor expression, and ERK1/2 and CAMKII signal transduction abnormalities.

Hyperpurinergia is a fundamental and treatable feature of the multisystem abnormalities in the poly(IC) mouse model of autism spectrum disorders. Antipurinergic therapy provides a new tool for refining current concepts of pathogenesis in autism and related spectrum disorders, and represents a fresh path forward for new drug development.