In a small, randomised Phase I/II clinical trial (SAT1), researchers at University of California San Diego School of Medicine say a 100-year-old drug called suramin, originally developed to treat African sleeping sickness, was safely administered to children with autism spectrum disorder (ASD), who subsequently displayed measurable, but transient, improvement in core symptoms of autism.
ASD encompasses a group of developmental disorders, often characterised by communication and language difficulties, repetitive behaviours and inability to socialise.
Writing in the Annals of Clinical and Translational Neurology, first author Robert Naviaux, MD, PhD, professor of medicine, paediatrics and pathology at UC San Diego School of Medicine and colleagues describe a novel double-blind, placebo-controlled safety study involving 10 boys, ages 5 to 14 years, all diagnosed with ASD.
Preclinical studies
Five of the 10 boys received a single, intravenous infusion of suramin, a drug originally developed in 1916 to treat trypanosomiasis (sleeping sickness) and river blindness, both caused by parasites. The other five boys received a placebo. The trial followed earlier testing in a mouse model of autism in which a single dose of suramin temporarily reversed symptoms of the neurological disorder.
The results in humans were equally notable, though the purpose of the SAT1 trial was fundamentally to test the researchers’ underlying theory about a unifying cause for autism and to assess the safety of suramin, which is not an approved treatment of ASD. In fact, there are no approved drugs to treat the core symptoms of ASD.
Trial results
All five boys who received the suramin infusion displayed improvements in language and social behavior, restricted or repetitive behaviors and coping skills. Assessment of improvements was based upon observational examinations and interviews using standardised tests and questionnaires, such as the Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2), the Expressive One Word Picture Vocabulary Testing (EOWPWT), the Aberrant Behavior Checklist (ABC), the Autism Treatment Evaluation Checklist (ATEC), the Repetitive Behavior Questionnaire (RBQ) and the Clinical Global Impression (CGI) questionnaire. To minimise misinterpretation of natural day-to-day variations in symptoms, parents were asked to mark a symptom as changed in the 6-week CGI only if the symptom lasted for at least one week.
The researchers found that ADOS-2 scores were improved in the suramin treatment group at six weeks, but not in the placebo group. Specifically, ADOS-2 scores improved by -1.6 points in the suramin group, but did not change in the placebo. Children who have a score of 6 or lower in ADOS-2 may have milder symptoms but no longer meet the formal diagnostic criteria for ASD. A score of 7 to 8 indicates the child is on the autism spectrum. Nine and above classifies the child as autistic.
Suramin treatment was also associated with improvements in the ABC, ATEC and CGI measurements, but not RBQ. The most changed behaviours, the authors said, were social communication and play, speech and language, calm and focus, repetitive behaviours and coping skills.
Participating families also reported benefits among the children who received suramin. "We saw improvements in our son after suramin that we have never seen before," said the parent of a 14-year-old who had not spoken a complete sentence in 12 years
Cell danger response
Naviaux, who is co-director of the Mitochondrial and Metabolic Disease Center at UC San Diego, believes that ASD – and several other chronic conditions, including chronic fatigue syndrome and some autoimmune disorders – are caused by metabolic dysfunction or impaired communication between cells in the brain, gut and immune system.
Specifically, this dysfunction is caused by abnormal persistence of the cell danger response (CDR), a natural and universal cellular reaction to injury or stress. "The purpose of CDR is to help protect the cell and jump-start the healing process," said Naviaux, by essentially causing the cell to harden its membranes, cease interaction with neighbours and withdraw within itself until the danger has passed.
"But sometimes CDR gets stuck," Naviaux said. "This prevents completio...
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