Mice, autism-like behaviour and antipurinergic therapy (and the 100 year old drug)

CC BY-SA by Wolfgang Lonien

CC BY-SA by Wolfgang Lonien

The past day, the news has been full of sensational headlines such as: Century-old drug reverses signs of autism in miceA 100-year-old drug corrects autistic social behaviors in lab tests and Autism symptoms ‘reversed’ in mice by 100-year-old drug. Our resident research analyst, Paul Whiteley Ph.D. puts this study into proper perspective.

Giving a particular type of mouse a single dose of the drug suramin, more routinely used to treat sleeping sickness, resulted in improvements in social behaviours and changes to other biological functions according to new research by Jane Naviaux and colleagues* based at the University of California San Diego School of Medicine in the United States. This study and a previous investigation by the same research group may provide some new directions for scientific inquiry into some cases of autism and schizophrenia.

Based on the maternal immune activation (MIA) model, whereby a state of elevated immune arousal is induced above and beyond that expected during pregnancy and potentially impacts on offspring developmental outcomes, researchers examined some of the biological processes potentially at work. A single dose of suramin, an antipurinergic agent which inhibits purinergic signaling, was administered at 6 months to offspring mice born to mothers presenting with MIA. In human years, this timescale would be equivalent to an adult receiving such an intervention at 30 years of age. The mice were then tested with various behavioural tasks to mimic facets of human development such as social and novelty preference and their results compared with control mice born to mothers without MIA and in receipt of either suramin or a placebo solution (saline).

Single-dose APT [antipurinergic therapy] with suramin completely reversed the social abnormalities in 6.5-month-old adults” the authors reported, based on their observations of the MIA offspring mice. Such a “social benefit” was even noted 5 weeks after the administration of the drug. Authors also examined the levels of suramin in mice and noted that “the brainstem showed significant suramin uptake”. This finding contrasted with those looking at other parts of the brain such as the cerebellum “consistent with an intact blood–brain barrier that excluded suramin from these tissues”. Allied to some detailed analysis of the biochemical pathways altered in MIA offspring animals and seemingly affected by the use of suramin, authors were able to build up quite an intricate picture of some of the biology of the MIA model and the effects of the drug.

Whilst this is interesting work, it is important to note that this is a study of mice, and mice who were subjected to a very specific set of circumstances in terms of the artificial induction of MIA during pregnancy. The authors observe that “no animal model can fully capture the complexities of human behavior” highlighting a major issue when extrapolating results from animal studies to humans. Further, they highlight the important fact that suramin is not a desirable drug to take long-term as a result of various side-effects which can occur such as renal failure and skin reactions.

They do however highlight how their results might further inform aspects of autism research and how their data may “create a fresh path forward for the development of newer and safer drugs” subject to appropriate replicative work.


* Naviaux JC. et al. Reversal of autism-like behaviors and metabolism in adult mice with single-dose antipurinergic therapy. Translational Psychiatry. 2014; 4: e400; doi:10.1038/tp.2014.33

Read more about this study here: http://questioning-answers.blogspot.com/2014/06/more-suramin-and-autism-mouse-findings.html