Research at UC San Diego shows important metabolic pathways in early autism development, opening new possibilities for early detection and medical treatments.
Discoveries indicate new options for early autism detection.
Scientists at the University of California San Diego School of Medicine have uncovered new information about the metabolic changes that happen from birth to the emergence of autism spectrum disorder (ASD) in childhood. They found that a small number of biochemical pathways are responsible for most of these changes, which could help with new strategies to detect and prevent autism at an early stage.
Robert Naviaux, M.D., Ph.D., a professor at UC San Diego School of Medicine, explained that at birth, the physical appearance and behavior of a child who will develop autism are the same as those of a typical child. In fact, in most cases, a child's fate with regard to autism is not determined at birth. The researchers are starting to learn about the governing dynamics that control the transition from risk to the actual appearance of the first symptoms of ASD. Early diagnosis opens up the chance for early intervention and the best outcomes.
Autism: A Complex Interplay of Factors
ASD is a developmental disorder characterized by challenges in socializing and communication, along with repetitive and/or restrictive behaviors. For most people with ASD, the condition is a significant disability, with only 10-20 percent of children diagnosed before 5 years of age being able to live independently as adults.
Although autism is known to have strong genetic risk factors, there are also environmental risk factors that contribute to the development and severity of ASD. Naviaux and other researchers are finding that the development of autism is influenced by the real-time interaction of these various factors. By studying the developmental biology of metabolism and how it differs in autism, new insights are emerging in ASD and other complex developmental disorders.
“Behavior and metabolism are linked – you cannot separate them,” added Naviaux.
To learn more about the early metabolic changes in children with autism, researchers studied two groups of children. One group consisted of newborns, in whom autism cannot be detected. The other group included 5-year-old children, some of whom had been diagnosed with autism.
When comparing the metabolic profiles of children in the group who were eventually diagnosed with autism to those who developed typically, they found significant differences. Of the 50 different biochemical pathways studied by the researchers, just 14 were responsible for 80 percent of the metabolic impact of autism.
New Insights Into Autism’s Biochemical Processes
The pathways that were most changed are related to the cell danger response, a natural and universal cellular reaction to injury or metabolic stress. The body has biochemical safeguards in place that can shut down the cell danger response once the threat has passed, and Naviaux hypothesizes that autism occurs when these safeguards fail to develop normally. The result is heightened sensitivity to environmental stimuli, and this effect contributes to sensory sensitivities and other symptoms associated with autism.
“Metabolism is the way that the brain, gut, and immune system use to talk to each other, and autism happens when the communication between these systems is changed,” said Naviaux.
The cell danger response is mainly controlled by adenosine triphosphate (ATP) the body’s chemical energy money. While these ATP-signaling paths do not develop normally in autism, they could be somewhat fixable with current pharmaceutical drugs. In 2017, Naviaux and his team finished early clinical testing for suramin, the only drug approved in humans that can aim at ATP signaling and which is usually used to treat African sleeping sickness.
Now, the researchers hope that by showing the specific ATP-related paths that are changed in autism, their work will help scientists create more drugs that aim at these paths to control the symptoms of ASD.
“Suramin is just one drug that aims at the cell danger response,” he said. “Now that we’re closely questioning how metabolism changes in ASD, we could be at the beginning of a drug rebirth that will make new choices for treatment that never existed before.”
Reference: 10 May 2024, Communications Biology.
DOI: /s42003-024-06102-y
Co-authors on the study include: Sai Sachin Lingampelly, Jane C. Naviaux, Jonathan M. Monk, Kefeng Li and Lin Wang at UC San Diego School of Medicine and Luke S. Heuer, Lori Haapanen, Chelsea A. Kelland and Judy Van de Water at University of California Davis This work was funded, in part, by Autism Speaks (grant 7274), the National Center for Research Resources (grant UL1TR001442), and through various philanthropic gifts.
