Sleeping sickness drug improves symptoms of ASD in children, offers insight into causes

A hundred-year-old drug used to treat sleeping sickness may transiently improve symptoms of autism spectrum disorder (ASD) and offers intriguing clues about the roots of the condition. 

In the small trial, Robert Naviaux and colleagues administered a single IV infusion of the drug Suramin to five boys with ASD. Five boys in a matched placebo group received a single IV infusion of saline. The study followed earlier experiments showing that suramin could reduce autistic symptoms in a mouse model of ASD. 

The researchers report that all five boys who received the suramin infusion showed improvements in language, social behavior, restricted or repetitive behaviors, and coping skills. Scores also improved on standardized tests, including the Autism Diagnostic Observation Schedule-2 (ADOS-2), the Autism Treatment Evaluation Checklist (ATEC), the Aberrant Behavior Checklist (ABC), and the Clinical Global Impression (CGI) questionnaire. 

Of the four nonverbal children in the treatment group, two said their first sentences approximately one week after receiving the suramin infusion. For all of the children, Naviaux says, “the benefit from speech therapy, occupational therapy, applied behavioral analysis and even from playing games with other children during recess at school skyrocketed.” 

Naviaux and his colleagues believe that suramin may work by correcting a metabolic dysfunction stemming from abnormal persistence of the cell danger response (CDR), which is a natural cell response to injury or other stresses. CDR causes cells to harden their membranes and stop communicating with other cells until a danger has ended. 

Naviaux says, “Sometimes CDR gets stuck. This prevents completion of the natural healing cycle and can permanently alter the way the cell responds to the world.” He and his team theorize that this abnormal persistence of CDR underlies autism and many other chronic childhood disorders. They believe that CDR, rather than being the sole cause of these disorders, combines with other factors such as genetics or environmental toxins. 

Naviaux says suramin works by inhibiting the signaling function of adenosine triphosphate, which is produced by the cellular mitochondria and released from cells to signal danger. He explains that suramin signals that “the cellular war is over, the danger has passed and cells can return to ‘peacetime’ jobs like normal neurodevelopment, growth and healing.” 

The researchers caution that their study was a very small trial, and their findings need to be confirmed by larger studies. They also stress, “Suramin is not approved for the treatment of autism. Like many intravenous drugs, when administered improperly by untrained personnel, at the wrong dose and schedule, without careful measurement of drug levels and monitoring for toxicity, suramin can cause harm. Careful clinical trials will be needed over several years at several sites to learn how to use low-dose suramin safely in autism, and to identify drug–drug interactions and rare side effects that cannot currently be predicted. We strongly caution against the unauthorized use of suramin.” 

Note: This study was partially funded by the Autism Research Institute.

Citations

“Low-dose suramin in autism spectrum disorder: a small, phase I/II, randomized clinical trial,” Robert K. Naviaux, Brooke Curtis, Kefeng Li, Jane C. Naviaux, A. Taylor Bright, Gail E. Reiner, Marissa Westerfi eld, Suzanne Goh, William A. Alaynick, Lin Wang, Edmund V. Capparelli, Cynthia Adams, Ji Sun, Sonia Jain, Feng He, Deyna A. Arellano, Lisa E. Mash, Leanne Chukoskie, Alan Lincoln, and Jeanne Townsend, Annals of Clinical and Translational Neurology, May 2017 (open access online). Address: Robert K. Naviaux, The Mitochondrial and Metabolic Disease Center, University of California, San Diego School of Medicine, 214 Dickinson St., Bldg. CTF, Rm. C102, San Diego, CA 92103, [email protected]. 

—and— 

“Researchers studying century-old drug in potential new approach to autism,” Scott LaFee and Heather Buschman, news release, UC San Diego Health, May 26, 2017.