Neurology

Mouse studies suggest stabilizing G-quadruplex DNA in FAM9B could help treat α-thalassemia X-linked intellectual disability syndrome (ATR-X). In brain samples from a mouse model of ATR-X, levels of a mouse homolog of FAM9B were higher than in samples from normal mice. In a mouse model of ATR-X, Gliolan aminolevulinic acid, a precursor of the G-quadruplex DNA-binding small molecule porphyrin, and a tool compound that stabilizes G-quadruplex DNA, decreased homolog mRNA levels in the brain and increased recognition memory and spatial memory compared with vehicle, and Gliolan decreased abnormal social behaviors. In a synaptic transmission assay in hippocampal slices from the model, Gliolan increased long-term synaptic potentiation, a marker of memory formation. Next steps could include identifying and testing additional stabilizers of FAM9B G-quadruplex DNA in humanized models of ATR-X...