Autism 'Reversed' In Mice For 5 Weeks, Thanks To 100-Year-Old Sleeping Sickness Drug
Geneticists from the University of California, San Diego, managed to reverse signs of autism in lab mice with help from a century-old African sleeping sickness drug, called suramin, a new study reports.
Building upon prior research into the complex interplay between genetics and the environment, the team found that attacking cells’ biology worked to produce key environmental changes in mice. These cellular changes ultimately reversed the animals’ reclusive, avoidant behaviors for just over a month. While incomparable to human models, which still demand clinical trials, the team believes their findings belie the assumption that autism is somehow permanent.
"Twenty percent of the known factors associated with autism are genetic, but most are not,” said Dr. Robert Naviaux, senior author and professor of medicine, pediatrics, and pathology, in a statement. “It's wrong to think of genes and the environment as separate and independent factors. Genes and environmental factors interact. The net result of this interaction is metabolism."
One of the telltale signs of autism, when looking at a cell, is its number of metabolic disturbances. Surrounding each cell in the body is a ring of metabolites and nucleotides. These substances broadly serve to regulate metabolism in the body. But when microbes or bacteria, threats to the cell, confront these metabolites, the cell’s outer layer stiffens. Communication between cells starts to degrade. Collectively, this process is known as the cell danger response.
"Cells behave like countries at war," Naviaux said. When there’s a threat, walls go up and countries stop communicating. In the case of neurons, he explains, this may mean fewer or too many connections. “One way to look at this related to autism is this: When cells stop talking to each other, children stop talking."
In the United States, because of a mix of genetic, environmental, or lifestyle factors, the autism rate in children is ascending with a troubling velocity. In the year 2000, the rate was roughly one in 150 children. By 2010, the rate had increased to one in 68. Boys are especially prone to autism diagnoses, as the rate pales in comparison to girls: one in 42 versus one in 189. Scientists have yet to pin down a conclusive cause — it’s likely an amalgam of many factors working together, Naviaux suspects — and research on the disorder, while robust, hasn’t bore much fruit.
In 2013, Naviaux authored a study that found that mice at 6 weeks old (15 years by human standards) saw a dramatic slide in autism-like symptoms when their cell danger response persisted. In his team’s latest study, mice at 6 months old (30 years) displayed the same behavior. But when they introduced suramin, which has been in use since the 20th century as a way to kill organisms responsible for African sleeping sickness, the mice’s autistic behavior stopped. Mazes no longer seemed unappealing. They joined other mice. Seventeen of the 18 major pathways that had been disrupted by the danger response had corrected or improved.
Migrating the drug from mice to humans isn’t so simple, however. Rodent tests far too often fail once they reach the human stage, for the sole reason that mice aren’t people. Our brains aren’t identical. Injecting prolonged doses of suramin into children, for instance, would almost certainly result in sweeping anemia. Purinergic receptors, those that interact with many autism-like behaviors via cells, aren’t only affected by suramin, however. The findings imply that other compounds could yield the same effect if they target these receptors in safer ways — provided that smaller doses of suramin fail human trials.
“The discovery that a single dose of medicine can fundamentally reset metabolism for weeks means that newer and safer drugs might not need to be given chronically,” Naviaux said. “Members of this new class of medicines might need to be given only intermittently during sensitive developmental windows to unblock metabolism and permit improved development in response to many kinds of behavioral and occupational therapies, and to natural play."
Source: Naviaux J, Schuchbauer M, Li M, et al. Reversal of autism-like behaviors and metabolism in adult mice with single-dose antipurinergic therapy. Translational Psychiatry. 2014.