Evolution of Organoids:
This year saw the debut of increasingly complex techniques for growing and analyzing brain organoids and other 3D tissue cultures.
For example, human cortical organoids can form functional connections in the brains of newborn rats and influence the animals’ behavior and feelings, one team reported in October, paving the way for the study of circuit disorders. According to work published in December, organoids grown from delicate individual nerve rosettes can capture the complexities of neural tube development. A gene expression sequencing technique in organoids, described this July, makes it possible to determine anew which cell types are affected by genetic variants associated with autism and how. And organoids with mutations in genes linked to autism may also serve as useful drug screens, researchers announced at Neuroscience 2022 in November.
Assembloids — conglomerates of organoids that model how two brain regions grow in tandem — can replicate differences in connectivity seen in humans with 22q13.3 deletion syndrome and mouse models of the condition, another team reported at Neuroscience 2022. And using the CRISPR gene-editing tool that assembloids may reveal which autism-linked genes help control the development and migration of interneurons, the November preprint reported.
In addition to brain organoids and assembloids, growing multiple mouse stem cell lines together in a dish can even give rise to “embryoids,” researchers announced in October. These models contain structures that mimic the heart and central nervous system and could pave the way for testing prenatal development in human embryos grown in the lab.
Cooperation – common and rare variants:
At least six large genetic studies this year have revealed how common and rare variants together influence the incidence and heterogeneity of autism.
Studies have shown that these variants in some cases act additively to make a person more likely to have autism, although they may contribute differently to the features of the condition. For example, autistic people with high numbers of common variants associated with the condition tend to have few co-occurring developmental disorders, and people who carry rare de novo mutations tend to have fewer common variants, according to a June study. another published at the same time. But autistic children with language delays inherit more frequent variants than autistic children with typical language development, according to unpublished work presented at the 2022 American Society of Human Genetics conference in October.
Rather than acting additively, common variants and a rare autism-linked deletion in chromosomal region 16p have similar effects on the expression of other genes in the region, an October study showed, suggesting that the cumulative effects of many common variants can sometimes equal a rare variant.
Two other studies published in August expanded the list of genes linked to autism and other developmental conditions and shed light on the role of rare inherited variants.
How to Get to the Mechanism Behind Autism’s Sex Bias:
Autism’s sex bias is one of the condition’s biggest mysteries: Why, researchers continue to ask, are boys and men nearly four times more likely to be diagnosed with autism than girls and women?
A combination of factors is likely at play, but biological differences are key, according to the 2022 findings. For example, the X chromosome may contain mutations that increase the likelihood of autism and have a disproportionate effect on boys, one study found in October. Compared to boys, girls are also less affected by common inherited variants associated with autism, another study reported in June. And in the womb, boys, unlike girls, tend to have patterns of cortical gene expression that match what is seen in the brains of adult autists, according to work presented at Neuroscience 2022 in November.
But it’s not just biology, according to a June study that attributes autism’s sex bias largely to how it’s diagnosed. This team found an equal ratio of autistic girls to autistic boys when they adjusted for differences in how boys and girls tend to perform certain tasks during different periods of development.
New translation efforts:
Despite our progress in understanding the biology of autism, few efforts have been made to translate these findings into treatment. Some industry players have taken steps to change that in 2022.
Several companies have taken up what has long been a challenge in the industry: designing treatments for idiopathic autism that are not thwarted by the heterogeneity of the condition. Switzerland-based Stalicla hopes to overcome this hurdle by using biological measures to define subgroups of autistic people and then design specific treatments for each. Spectrum reported in June. Iama Therapeutics, an Italian start-up Spectrum profiled in October, is instead betting on a single treatment with a known mechanism and then trying to identify the population of autistic children that would respond best to it.
Therapeutics designed for people with rare genetic conditions associated with autism largely avoid the problem of heterogeneity and have also advanced in 2022. Several clinical trials are underway for drugs that increase the expression of a key gene associated with Angelman syndrome, for example. And treatment for Dravet syndrome, a genetic condition that can cause fatal epilepsy, reduced the number of seizures in children with the syndrome in a clinical trial this year. These trials often foster strong relationships between researchers and family groups; in some cases, researchers study their own child’s rare condition, e.g Spectrum reported in profile in July.
Profound Autism:
In December 2021, the committee organized Lancet the formally recommended term for autistics who require continuous, lifelong support: profound autism. This designation sparked a conversation that caught the attention of the advocacy and research communities throughout 2022.
The committee intended to “bring attention to the fact that these children and adults do exist and that they need different services,” said co-chair Catherine Lord. Spectrum. Many welcomed the approach — including the Autism Science Foundation, which has awarded $35,000 in new grants to study deep autism — but others saw it as potentially isolating some autistics from the larger community.
In February, an open letter with more than two dozen signatures described the term as “highly problematic”. November editorial on Spectrum Autism Science Foundation President Alison Singer, arguing in favor of the term, has received both support and opposition. Many advocates see the designation as an opportunity to involve more high-need autistic people in research. But its creation is inconsistent with the neurodiversity paradigm and eschews the expertise of autistic people, developmental psychologist Sue Fletcher-Watson argued in response to the editorial.
Cite this article: https://doi.org/10.53053/JWJR9206
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