Neurology

Cell culture studies identified a pyridocarbazole-based inhibitor of disease-associated hairpin forms of GGGGCC repeat expansions in C9orf72 that could help treat ALS. In HEK cells, an optimized version of a previously reported pyridocarbazole-based compound bound the hairpin form of the eight-GGGGCC-repeat transcript with a K_d of 0.26 μM. In HEK cells expressing a 66-repeat expansion of GGGGCC, the compound inhibited the generation of poly-glycine-proline, a toxic repeat-associated non-ATG (RAN) translation product, with an IC₅₀ of 1.6 μM. Next steps could include testing the compound in animal models of ALS harboring the C9orf72 expansions...