- An in-depth review of antipurinergic therapy for autism
- The SAT1 clinical trial, published in Annals of Clinical and Translational Neurology
- Parent statements
- Questions and answers with Dr. Naviaux
- Cautionary statement about suramin
- A physician’s poem of hope
- UCSD website with content about the suramin clinical trial
- N of One website with content about the trial
- UCSD Triton Magazine Story, Fall 2017
We think of autism as a neurometabolic and neuroimmune syndrome that is caused by the pathological persistence of the cell danger response (CDR). Both genes and environment can activate the CDR, which consists of about 30 metabolic pathways that work together to defend the cell against danger or stress3,5. When activated during early child development, the CDR can have a significant impact on behavior and brain development. The CDR is maintained by increased purinergic signaling6-8 that results from the release of nucleotides like ATP, ADP, UTP, UDP, and other metabolites that trace to mitochondria in cells under stress. Purinergic receptors are widely distributed on every cell type in the body. When activated, they can signal danger or trigger inflammation and pain. Nucleotides like ATP are co-neurotransmitters and neuromodulators at every synaptic junction studied to date. They are particularly important for cells in the nervous system, immune system, and the GI tract, which in turn, affects the gut microbiome. Suramin is a non-selective inhibitor of purinergic signaling, an antipurinergic drug, or APD for short. Suramin works in several ways to inhibit purinergic signaling. One way is to act as a competitive inhibitor of ATP binding to cell surface receptors. Another way is to block the release of intracellular ATP through pannexin-P2X7 channels into the extracellular space. Working in these ways, suramin sends an “all’s clear” signal to the cell. One way to think about suramin action is as “molecular armistice therapy”—a metabolic signal that the danger has passed and cellular resources can be directed away from defense and returned to “peace time” activities like normal neurodevelopment, healing, and growth.
We have just completed the first clinical trial to test the safety and efficacy of suramin in children with autism (https://clinicaltrials.gov/ct2/show/NCT02508259).
- Naviaux, R.K. Antipurinergic therapy for autism—an in-depth review. Mitochondrion. PMID: 29253638, 2017.
- Naviaux, J.C., et al. Antipurinergic therapy corrects the autism-like features in the Fragile X (Fmr1 knockout) mouse model. Molecular Autism 6, 1 (2015).
- Naviaux, R.K., et al. Reversal of autism-like behaviors and metabolism in adult mice with single-dose antipurinergic therapy. Translational Psychiatry. PMID: 24937094, 2014.
- Naviaux, R.K. Metabolic features of the cell danger response. Mitochondrion 16, 7-17 (2014).
- Naviaux, R.K., et al. Antipurinergic Therapy Corrects the Autism-Like Features in the Poly(IC) Mouse Model. PloS One (2013).
- Naviaux, R.K. Oxidative shielding or oxidative stress? J Pharmacol Exp Ther 342, 608-618 (2012).
- Naviaux, R.K. Mitochondria and Autism. in The Neuroscience of Autism Spectrum Disorders (eds. Buxbaum, J.D. & Hof, P.R.) 179-193 (Academic Press, Elsevier, Waltham, MA, 2012).
- Burnstock, G. Introduction to purinergic signalling in the brain. Advances in experimental medicine and biology 986, 1-12 (2013).
- Burnstock, G. Purinergic mechanisms and pain–an update. Eur J Pharmacol 716, 24-40 (2013).
- Burnstock, G. Discovery of purinergic signalling, the initial resistance and current explosion of interest. British journal of pharmacology 167, 238-255 (2012).