Anti-parasitic Drug Found To Reverse Autism-like Symptoms In Mice

Last week, UCSD researchers, led by Dr. Robert K. Naviaux, professor of genetics at the UCSD School of Medicine, published a study that made major advances toward a cure for autism spectrum disorders. Using suramin, an antimicrobial drug first developed to treat trypanosomiasis, also known as “African Sleeping Sickness,” in 1916, Dr. Naviaux’s group observed substantial improvements in reversing ASD symptoms amongst mice.

Fragile X-genetics mice, which are commonly used to study autism, were administered a weekly injection of either suramin or a saline placebo. After one month, researchers found normal social behavior to be restored in the suramin-treated mice, as well as improved metabolism responses in their cells and brain synaptosomal structures.

This study, considered a test of genetic ASD-causing factors by Naviaux, follows in the wake of another study the group published in June of last year, which used maternal immune activation mice to study the environmental factors that lead to ASD. In both cases, mice who had developed an autism-like disorder shortly after birth were examined. A remarkable discovery was made: In the 6-month-old mice — equivalent in age to a human adult of 30 years — clear signs of reverting back to normal social behavior were observed within minutes of receiving a single dose of suramin.

Naviaux told the UCSD Guardian that he was led to the idea of using suramin to treat autism after first discovering an overabundance of extracellular ATP to be one of the leading causes of the disorder. Cells naturally generate ATP as a vital source of internal energy, but when this chemical is expressed outside the barrier of the cell, it can bind to certain neural receptors and cause inflammations that block regular early development. Suramin, because of its molecular structure, can compete with extracellular ATP for a place to bind to the neural receptors, thus eliminating any possibility for damage.

Because no one else had ever looked at suramin as a possible solution to autism, Naviaux said he had to develop new concepts.

“I surveyed the world’s pharmacopoeia,” Naviaux said. “I looked specifically for drugs that would inhibit extracellular ATP function, and there were none available except suramin. That was the only one, and even then [suramin] had never been used before in this way.”

Naviaux discovered that the underlying threat of ASD is one of the body’s naturally-occurring defense mechanisms, which he named cell danger response, or CDR. When cells sense incoming stress — either from environmental factors like viral infections or from unusual genes they possess that tell them to initiate a defensive response — they alter their basic functions in an attempt to block out the perceived threat.

“One of the first things that happens when cells go to war is what happens when nations go to war: They harden their borders,” Naviaux said. “From a cell’s point of view … [they] stiffen their membrane, so now a virus has a harder time penetrating the defenses of the cell.”

CDR defines a total of 30 metabolic functions that shift within cells when they perceive danger. The message to engage in CDR is sent by high levels of extracellular ATP, and for children with ASDs who are found to exhibit such abnormal levels, their CDR can be left in an activated position indefinitely, as Naviaux explained.

“All of this is really important because another thing that happens when nations go to war is that they don’t trust their neighbors across the border, and they don’t talk to or exchange resources with their neighbors,” Naviaux said. “And when cells don’t talk to each other, children stop talking.”

Naviaux illustrated the isolating effects caused by autism with the metaphor of a child who wants to go outside and play with others but is trapped behind a frosted window.

“A lot of parents will describe that there are certain times when it seems like the glass is broken and the child comes out and they can actually speak and interact,” Naviaux said. “But then they’ll fall back behind the veil for the majority of time, and they’ll be afraid to interact socially, and they won’t be able to talk and they’ll have many different behaviors that — from the point of view of the child — are defending them from an overstimulating and potentially hostile environment. They don’t interpret it that way, but their cells do.”

In a metabolic analysis from Naviaux’s most recent study involving suramin, 17 of the biochemical pathways that represent CDR in both mice and in humans were identified, which strongly suggests an improvement in ASD symptoms. The other good news is that suramin has been found to provide benefits that last longer than the amount of time it remains within the body, as Naviaux explained.

“[This] allows the possibility for children to amplify the effects of the drug treatment by being able to engage in natural play that, in their previous state, they never would have been able to do,” Naviaux said. “Those kinds of things, [such as] playing with a brother or sister or friend, are actually the most potent kind of neural development known to man.”

The next step in suramin-related ASD research will be a clinical trial: 20 boys, of ages ranging from 4 to 9 with ASD in the San Diego area will be administered the drug through an IV infusion. Naviaux expects to see changes in the beginning stages of the experiment lead to improvement in ASD symptoms, including speech and willingness to interact socially.

What was witnessed in animal models, however, is that after six weeks, the immediate benefits of suramin lost potency, and subjects eventually returned to previous social patterns.

In addition, Naviaux stated that he is seeking to develop a treatment for ASD that does not rely heavily on medication.

“I’d like to start a new chapter in pharmacology,” Naviaux said. “One that is no longer restricted to benefits that are only happening when a drug interacts with its receptor, and whenever the drug is gone, there’s no more benefit.”