Using antisense oligos to plumb rare genetic conditions, and more

Rare form: Two new studies use antisense oligonucleotides (ASOs) to investigate mechanisms of autism-related conditions. One paper reports that ASOs targeting SCN2A variants reduced seizures and improved language and motor skills in two children with developmental and epileptic encephalopathies. The other study, a preprint, used ASOs to reveal molecular pathways from a truncated ASXL3 gene to broader genomic and translational changes observed in Bainbridge-Ropers syndrome. Studies of rare genetic disorders such as these often rely on data from very few participants, as The Transmitter has previously covered, to develop bespoke treatment strategies.

Autism research spotted this week:

• “Visual cortical response variability in infants at high familial likelihood for autism” bioRxiv
• “Autism spectrum disorder incidence by age and sex in a US health care system, 2016 to 2024” JAMA Network Open
• “A multimodal interrogation of Broca’s area in the pediatric and adult human brain” bioRxiv

• “Functional covariance modes reveal aligned fetal and neonatal brain functional connectomes” bioRxiv
• “RA Capital backs upstart rival to Ultragenyx and Ionis in rare brain disease” STAT
  See also: “What next for Angelman?”
• “Modeling phase separation dynamics of SYNGAP and PSD-95 in postsynaptic densities” bioRxiv
  See also: “How microscopic ‘condensates’ in cells might contribute to autism”