Old drug points to promising new direction for treatment of autism

Posted By on May 28, 2017

A small trial involving 10 boys with autism spectrum disorder showed promising results from treatment with a drug called suramin, which was originally developed 100 years ago to treat African sleeping sickness, a parasitic disease. Boys who received a single dose of the drug showed measurable, though not permanent, improvements in autism spectrum disorder symptoms.
[new treatment for autism]
New research shows that a drug developed over a century ago could successfully treat autism.

A report on the trial – led by the University of California-San Diego (UCSD) – is published in the Annals of Clinical and Translational Neurology.

Autism spectrum disorder (ASD), or autism, is a developmental disability with a cluster of behavioral symptoms that typically surface in childhood and generally affect social interaction and communication.

ASD is considered a complex, wide-spectrum disorder because the many symptoms can vary in combination and intensity. For this reason, no two people with ASD will have exactly the same symptoms.

Some of the behavioral symptoms of ASD include:

  • difficulty making eye contact
  • delayed language development
  • difficulty holding a conversation
  • intense or obsessive interests
  • problems with planning and reasoning
  • poor motor skills
  • difficulty processing sensory signals

According to the Centers for Disease Control and Prevention (CDC), ASD affects around 1 in 68 children in the United States and occurs in all socioeconomic, racial, and ethnic groups. However, it is about 4.5 times more common in boys than in girls.

There is no single cause of ASD, but it is thought that a combination of genetic and environmental factors is involved, ranging from pollutants to viral infections and pregnancy complications.

‘Cell danger response’ as a unifying theory of ASD

Robert K. Naviaux, a professor of medicine, pediatrics, and pathology at UCSD School of Medicine and first author of the new study, believes that the idea of an abnormal “cell danger response” may offer a unifying theory for the development of ASD.

The cell danger response is a normal signal sent out by all cells when they suffer injury or stress. Its purpose, says Prof. Naviaux, “is to help protect the cell and jump-start the healing process.” The signal causes the cell to stiffen its cell walls, stop talking to other cells, and withdraw until the threat subsides.

However, Prof. Naviaux explains that the cell danger response “can get stuck” and stop the completion of the cell’s healing cycle. The cell persists in the threat response state, which can “permanently alter the way the cell responds to the world.”

The effect at the molecular level is to disrupt the chemistry of cell equilibrium and cause chronic disease. Prof. Naviaux says that “when this happens during early child development, it causes autism and many other chronic childhood disorders.”

Cells activate the cell danger response by releasing a small molecule from their energy-making compartments, or mitochondria. The release of this molecule is what acts as the danger signal, and it keeps being released as long as the cell danger response is active.

Suramin blocks the ability of the small molecule to release the danger signal. The effect, says Prof. Naviaux, is to signal that “the cellular war is over, the danger has passed and cells can return to ‘peacetime’ jobs like normal neurodevelopment, growth, and healing.”

The drug was originally developed in 1916 by the German firm Frederich Bayer and Co. for treating diseases caused by trypanosome parasites, such as those that cause African sleeping sickness and river blindness.

Trial tests suramin safety and cell danger response theory

For their small study – which took the form of a randomized, double-blind, placebo-controlled phase I/II clinical trial involving 10 boys, all aged between 5 and 14, who were diagnosed with ASD – the team tested the effect of a single dose of suramin on symptoms of ASD.

The aim of the trial was to find out whether the cell danger response theory might explain the development of ASD and to assess the safety of suramin, which is not approved for the treatment of ASD. An earlier trial that tested the drug on mice had found that a single dose “temporarily reversed” symptoms of ASD.

The boys were randomly assigned to receive either a single intravenous transfusion of suramin, or a placebo.

The results showed that all five boys who received the active drug showed measurable improvements in ASD symptoms not seen in the placebo group. The improvements were specifically in speech and language, social communication and play, coping skills, calm and focus, and repetitive behavior.

The researchers used a battery of standardized tests and interviews to measure the improvements. When these involved parent observations, the team only counted a change as an improvement if it persisted for at least a week. This was to rule out any fluctuations in day-to-day behavior that may have occurred anyway.

Prof. Naviaux says that there were four non-verbal children in the trial: two aged 6 and two aged 14, with one of each age having been assigned to the drug group and the placebo group.

“The 6-year-old and the 14-year-old who received suramin said the first sentences of their lives about one week after the single suramin infusion,” he notes. “This did not happen in any of the children given the placebo.”

Improvements were transient

The team reports that while the children were on suramin, there was a dramatic improvement in the benefits they derived from the speech therapy, occupational therapy, and other programs that they were taking part in.

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