There are currently no FDA-approved drugs to treat the core symptoms of autism spectrum disorder (ASD).
But new findings published in the Annals of Clinical and Translational Neurology may help open the door to novel treatment options while shedding light on the underlying causes of ASD.
In small phase I/II clinical trial at the University of California San Diego (UCSD) School of Medicine, researchers assessed the effects of a drug called suramin among children with ASD.
Ten boys with autism, ages 5 to 14 years, took part in this double-blind, placebo-controlled study.
Five boys each received a single injection of suramin, while the remaining five received placebos.
All five participants that received suramin showed temporary but promising improvements in their language and behaviour, with no serious side effects reported.
“We had no expectations that there would be any statistically significant outcomes in core behaviours in all five children,” Dr Robert Naviaux, first author, and a professor of medicine, paediatrics, and pathology at UCSD, told Healthline. “But to our surprise, we found that the average child in the suramin group had a 1.6-point improvement in their ADOS [Autism Diagnostic Observation Schedule] comparison scores after six weeks, while the placebo group had no change.”
“To put that in context,” he added, “autism spectrum disorder is defined as having an ADOS score between 7 and 10, with 10 being the highest.
The average child in our study had an ADOS score of 8.6. Then after six weeks, the average was 7.0.”
Among participants who received suramin, the study authors found changes in speech, language, social communication, repetitive behaviours, coping skills, calmness, and focus.
For example, two nonverbal boys who were treated with the drug spoke the first full sentences of their lives about a week after receiving injections.
These effects wore off after several weeks, suggesting that multiple doses of the drug may be needed.
To learn if these findings can be safely reproduced, larger follow-up studies are required.
Shedding light on the causes
According to the Centers for Disease Control and Prevention (CDC), ASD affects an estimated 1 in 68 children in the United States.
It has so single known cause, which poses barriers to developing treatments.
“One of the things that’s held the field back is that there’s so much heterogeneity, so much difference, from one person to another,” Dr Andrew Zimmerman, a paediatric neurologist at the University of Massachusetts Medical School, told Healthline. “It’s been hard to study because you can’t narrow it down to simple categories. There are tremendous overlaps from one patient to another, but there are different clinical characteristics, biochemical characteristics, and genetic characteristics.”
He suggested the results of Naviaux’s suramin study might help researchers navigate this heterogeneity, by providing insight on how ASD develops.
Naviaux said that for some children, ASD results from a treatable metabolic syndrome that is caused by an abnormal persistence of the cell danger response (CDR).
The CDR is a natural reaction that cells have to injury or stress. It causes their membranes to harden and limits their interactions with other cells, until the perceived threat has passed.
The CDR can sometimes get stuck, causing cells to act as if they are in danger, even after the initial threat has passed. This may contribute to the development of many chronic diseases, including ASD, Naviaux said.
The CDR is maintained by a mechanism known as purinergic signalling, which happens when small molecules bind to purinergic receptors, acting as an alarm signal.
Suramin is an antipurinergic drug that prevents these molecules from binding to purinergic receptors, putting a stop to the CDR.
The positive effects that suramin had on children and youth with ASD lends support to Naviaux’s theory that abnormal cell danger response plays a role in the disease.
“There are a lot of tracks that people are working on, and this is one very exciting track,” Zimmerman noted. “I think this is a new era in looking at the metabolic connections of the cell.”
On-going research is needed
To assess the effects of multiple doses of suramin over a longer time period, Naviaux plans to conduct larger follow-up studies.
“We’ll have to do the next trial with 40 to 60 children at a couple different sites,” he said. “That will be both a safety and efficacy study. We’ll look at 40 to 60 children and ask the question, are three doses of suramin given over three months both safe and effective in treating the core symptoms of autism?”
Before Naviaux can begin that study, he needs to attain funding.
Suramin is a low-cost drug that is unlikely to reap large profits for the pharmaceutical companies that typically fund drug trials.
“Normally, big pharma supports the tens of millions of dollars it costs for clinical trials because they’re the ones that will benefit after the FDA approves it,” Naviaux noted. “But we don’t have that. In fact, with the low doses that we use, we could in principle treat an 8-year-old child for a whole year with $27 worth of suramin.”
Naviaux’s first trial was funded in large part through philanthropic donations. He suspects the next trial will also rely on grassroots support.
In the long term, he hopes this research can help inform safe and effective treatment strategies, not only for autism but for many other health conditions too.
“What we’re learning from autism is also giving us important insights into deep biology and other chronic complex diseases, like chronic fatigue syndrome, post-traumatic stress disorder, major depressive disorder, and many more,” he said.