Promising autism drug needs more study
Trial will focus on boys, since they’re more prone to develop the condition
An experimental autism drug will be more extensively tested next year by researchers at UC San Diego, where a small clinical trial showed early signs of effectiveness in 2017.
The trial will be conducted at UCSD and UCLA. It will test the drug on 20 boys, who will get three infusions over three months. Each will be paired with a similar boy in a control group who won’t get the drug, for a total of 40 boys.
It’s tentatively expected that boys from 5 to 15 will take part, said Dr. Robert Naviaux, the UCSD researcher leading the study. The trial focuses on boys because they are far more prone to develop autism than girls. If girls were included, the trial size would have to be doubled, making it prohibitively expensive, he said. But girls are to be included in later testing.
The drug is suramin, a century-old medicine for sleeping sickness. In the first trial, five boys given a single infusion of suramin showed noticeable improvement in social interaction and function. That improvement faded over two months, although some skills, such as tying shoelaces and learning new reading words, remained.
Treated boys began achieving new milestones, such as actively engaging in new language, social games like tag, trying new foods, and taking on new interests in music, dance, sports and science. Two of the boys who were non-verbal spoke the first sentences of their lives after about one week.
Five control boys who weren’t given the drug didn’t show significant improvement.
Naviaux is also leading a separate study that seeks to predict autism risk at birth. Numerous efforts have been underway to find such predictive evidence, because the earlier children at risk are identified, the better the results of therapy.
The study will examine results from routine tests given at birth and look for biochemical signatures of a metabolic imbalance related to autism, along with family history. A total of 250 families are being sought.
To qualify, children must now be between 3 and 10 years old, born in California of a normal term pregnancy, and not readmitted to the hospital in the first month after birth. In addition, children must either have been diagnosed with autism spectrum disorder, or a typically developing child not taking prescription medications.
The screening and enrolment can be performed online; there’s no need for a visit.
Both of these studies arise from Naviaux’s research into metabolic dysfunction as a possible cause of autism and chronic diseases. His hypothe- sis is that the normal cellular danger response, or CDR, gets stuck, leaving cells in a malfunctioning state. This response is part of a natural healing process injured cells go through.
Naviaux researched the pharmacology of over 2,000 drugs already approved to find those that might remove the CDR roadblock he found in autism. Suramin was the only drug that had the desired activity.
The upside is that already approved drugs can be more quickly repurposed and entered into clinical testing. The downside is that companies are reluctant to fund the testing of a drug whose patent has long expired. The trial with suramin was funded entirely with private donations, and Naviaux has been looking for money to run the new trial.
Biotech investors have formed a new company to carry out the more advanced trial of suramin in autism, Naviaux said. The company will also manufacture the drug. For now, the company isn’t disclosing its name, he said.
Meanwhile, Naviaux has published new research about the cell danger response, describing it in more detail. The study, published in the journal Mitochondrion, breaks down the cellular danger response into three stages, each of which must be completed before the next one can begin.
This response is a universal response to injury, he said, whether from a cut, a cold or a heart attack. And it’s closely linked to mitochondria, cellular energy-producing organelles.
Mitochondrial dysfunction has been linked to a number of chronic diseases, including Type 2 diabetes, Parkinson’s disease and Alzheimer’s disease. “We call them CDR1, CDR2 and CDR3,” Naviaux said of the three stages. “These are an intrinsic part of the natural healing cycle. We’re trying to organize the molecular details, in a way that allows us to study individual steps of the healing process in an objective, scientific way.”
Suramin targets this response across all three cycles, by inhibiting release of an energy-carrying molecule called ATP outside the cell. ATP is produced inside mitochondria, and its presence outside the cell is a sign of cellular damage.
The Mitochondrion paper can be found at j.mp/mitocdr.
For information on the studies, go to naviauxlab.ucsd.edu.