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Human Brain Organoid Model Provides Autism Insights

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Autism spectrum disorders (ASD) comprise a complex collection of developmental disabilities that can cause considerable behavioral, communication and social challenges. While there are likely many causes of ASD, including biologic, genetic and environmental factors, most ASD cases lack a clear origin. 

Researchers at Johns Hopkins Bloomberg School of Public Health recently used a human brain organoid model to show that genetic and environmental factors may interact to contribute to increased prevalence of autism. It is key that this research was performed in a human relevant model, as traditional experiments involving animals are not only expensive and fraught with ethical concerns, but data from such research may also not translate to humans. 

The researchers discovered that a common pesticide thought to contribute to developmental neurotoxicity and autism risk lowered levels of a protein important for brain development. Mutations in the gene that encodes for this protein have been identified as possible genetic risk factors for autism. 

The researchers also examined other molecules whose levels are different in patients with ASD. The researchers found that levels of these biomarkers were also changed in organoids exposed to the pesticide, in organoids that had reduced levels of the protein important for brain development, and in organoids with the reduced protein level that had been exposed to the pesticide. 

“This is a step forward in showing an interplay between genetics and environment and its potential role for autism spectrum disorder,” Dr. Lena Smirnova, principal investigator of the study, noted. “We showed that changes in these organoids reflect changes seen in autism patients.”

Importantly, the model and approach used in this study can be used in future experiments designed to examine gene-environment interactions in a human relevant way. 

“The use of three-dimensional, human-derived, brain-like models like the one in this study is a good way forward for studying the interplay of genetic and environmental factors in autism and other neurodevelopmental disorders,” according to Dr. Thomas Hartung, a lead researcher of this study and mentor to a former NAVS/IFER graduate fellowship recipient Georgina Harris

We will keep you posted on future developments with this model and the ways that in vitro models like organoids reduce and replace animal use in science. 

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Source: 

Center for Alternatives to Animal Testing press release, “Brain Organoid Study Highlights Potential Role of Genetic and Environmental Interaction in Autism Spectrum Disorder,” July 14, 2021.