New research evaluating the effects of a century-old drug on mouse models of autism spectrum disorder (ASD) provides a potentially important clue about how ASD develops. The study, published in the January 2015 issue of Molecular Autism, demonstrates that suramin, a drug approved in 1916 to treat African sleeping sickness, restored normal social behavior and improved brain function in mice. The mice were genetically engineered to have symptoms similar to some of those seen in people with ASD.

The finding builds on previous work by the same team showing that suramin also relieved symptoms in a different mouse model of ASD, in which mice exposed to an environmental risk showed autism-like antisocial behaviors. (The environmental exposure occurred when the mice were still in the womb and the immune systems of their mothers were activated by an infection.) Suramin, known to scientists as an antipurinergic therapy, provides a fresh path to examine two possible mechanisms––genetic and environmental––that are thought to be involved in causing ASD.

Whether environmental or genetic, “antipurinergic therapy with suramin corrected the abnormalities that characterized each model of the disorder,” reported the researchers, who included 2004 NARSAD Young Investigator, Susan B. Powell, Ph.D., of the University of California (UC), San Diego. “This suggests we’ve discovered a mechanism that helps bridge the [proposed] genetic and environmental causes of autism,” said team leader Robert K. Naviaux, M.D., Ph.D., also of UC San Diego.

This potentially common “root” mechanism, Dr. Naviaux explains, is the cellular danger response (CDR), a protective metabolic reaction that is engaged when a threat is detected.  Suramin may relieve ASD symptoms precisely because the CDR is important in both models of ASD. The “threat” that activates the CDR could be an infection––as seen in the environmental mouse model––or a mutation (gene change), as shown in the genetic model. The mutation in the genetic model occurs in a gene known to cause Fragile-X syndrome, a defect often linked with ASD.  

In CDR, cells shut down and put up barriers to the perceived danger. Communication between cells can be reduced as a result, and this breakdown in communication is what the researchers think may be interfering with brain function in the development of at least some ASD symptoms.  

The researchers warn that suramin may be toxic in humans after prolonged use; they are not suggesting it is a potential autism therapy. What is exciting about the research, says Dr. Naviaux, is that it provides new insight into the origins of autism as well as the potential value of some form of antipurinergic therapy, other than suramin.

Read the abstract.