Autism Risk Genes
A recent post by Jessica Lau in the Harvard Gazette (February 2, 2022) is titled “Different autism risk genes, same effects on brain development.” I honestly don’t understand all of the science here, but it seems potentially very exciting. They begin by noting that numerous genes have been implicated in autism spectrum disorders, but researchers at Harvard and MIT, “have found that three different autism risk genes actually affect similar aspects of neural formation and the same types of neurons in the developing human brain. By testing the genetic mutations in miniature 3D models of the human brain called ‘brain organoids’, the researchers identified similar overall defects for each risk gene, although each one acted through unique underlying molecular mechanisms.” Their findings are published in Nature.
I am again quoting directly:
Much effort in the field is dedicated to understanding whether commonalities exist among the many risk genes associated with autism. Finding such shared features may highlight common targets for broad therapeutic intervention, independent from the genetic origin of disease. Our data show that multiple disease mutations indeed converge on affecting the same cells and developmental processes, but through distinct mechanisms. These results encourage the future investigation of therapeutic approaches aimed at the modulation of shared dysfunctional brain properties,” said senior author of the study Paola Arlotta, who is the Golub Family Professor of Stem Cell and Regenerative Biology at Harvard University and an institute member in the Stanley Center for Psychiatric Research at the Broad Institute.
They use organoid models of the human cerebral cortex, the models starting off as stem cells, which then “grow into a 3D tissue that contains many of the cell types of the cortex, including neurons that are able to fire and connect into circuits.” Here’s another lengthy section of the post:
“It is puzzling how the same autism risk gene mutations often show variable clinical manifestations in patients. We found that different human genomic contexts can modulate the manifestation of disease phenotypes in organoids, suggesting that we may be able to use organoids in the future to disentangle these distinct genetic contributions and move closer to more a complete understanding of this complex pathology,” Arlotta said.“Genetic studies have been wildly successful at identifying alterations in the genome associated with autism spectrum disorders and other neurodevelopmental conditions. The difficult next step on the path to discovering new treatments is to understand exactly what these mutations do to the developing brain,” said Steven Hyman, who is a Harvard University Distinguished Service Professor of Stem Cell and Regenerative Biology, the director of the Stanley Center at the Broad, and a Broad Institute core member.
I wanted to share this information in large part because it may help diagnosticians and therapists to communicate to parents not only that autism spectrum disorders are diverse and complex, but also that intense multidisciplinary efforts are underway to better understand possible therapeutic interventions.