New approach to combat a leading cause of autism spectrum disorders

By generating models derived from the cells of patients with FXS and exposing the models to different laboratory conditions,the researchers discovered conditions that induce a strong repeat contraction and full FMR1 reactivation. The conditions required the presence of inhibitors of two kinases called MEK and BRAF.

Inhibiting these enzymes led to enhanced production of special nucleic acid structures called “R-loops” formed between DNA and RNA, which cells see as DNA damage and therefore trigger repair mechanisms to fix the problem. The cells’ repair mechanisms then excise the expanded CGG repeats to achieve more normal CGG levels, enabling cells to re-express the crucial FMR1 gene.

Reference :Site-specific R-loops induce CGG repeat contraction and fragile X gene reactivation,Cell

DOI 10.1016/j.cell.2023.04.035