Autism in Three Dimensions: Using Brain Organoids to Study Potential Gene-Environment Interactions

• Published in: Environmental health perspectives Vol. 129; no. 10; p. 104003
• Main Author: Schmidt, Silke
• Format: Journal Article
• Language: English
• Published: United States National Institute of Environmental Health Sciences 01.10.2021; Environmental Health Perspectives
• Subjects: Animal models; Autism; Autism Spectrum Disorder - genetics; Autistic Disorder - genetics; Brain; Brain research; Cell lines; DNA helicase; Drug development; Environment models; Environmental health; Environmental risk; Gene-Environment Interaction; Genes; Heterogeneity; Humans; Hypotheses; Mutation; Neurotransmitters; Organoids; Patients; Pesticides; Proteins; R&D; Research & development; Risk analysis; Risk factors; Science Selection; Toxicants; United States > US; Massachusetts
• ISSN: 0091-6765; 1552-9924
• DOI: 10.1289/ehp10301

The clinical heterogeneity of autism spectrum disorder (ASD) makes it difficult to match treatments to patients.1 The unique nature of ASD in humans has also hampered the use of animal models in drug development.2,3 Brain organoids, “miniature brains” derived from human cells, have emerged as a promising alternative strategy for understanding ASD.3,4 A recently published study in Environmental Health Perspectives5 suggests these organoids may also be well suited for modeling the gene–environment interactions that have long been suspected of increasing ASD risk.6 [Image omitted - see PDF] Lena Smirnova and colleagues compared brain organoids containing a normal version of CHD8, the gene encoding chromodomain helicase DNA binding protein 8, with those containing the high-risk ASD mutation CHD8+/−. No environmental risk factor for ASD has been as strongly implicated as the gene mutations, but CPF is a known neurodevelopmental toxicant that was banned from most household uses more than 20 years ago in the United States.9 A renewed ban from use on food crops is expected to take effect in early 2022.10 “Although the CHD8 mutation is highly penetrant, and patients who carry it share certain clinical features, the severity of their symptoms can vary,” says Smirnova. Because the current study did not use cell lines from patients with the CHD8 mutation, the researchers could not test their hypothesis directly.