Fig. 4.

Proposed therapeutic approaches for C9orf72 disease. At this point, 2 therapeutic approaches have been proposed and partially demonstrated for C9orf72 disease. First, an antisense oligonucleotide approach whereby the introduced molecule forms a double-stranded complement with the transcribed repeat sequence and thus targets it for degradation by RNAse H. This has been reported to reverse the formation of RNA foci and rescue certain molecular phenotypes. Second, a small molecule approach targeting the secondary structure of GGGGCC repeat RNA, which is thought to be in equilibrium between a hairpin and a G-quadruplex conformation, has been shown to disrupt both formation of RNA foci and translation of dipeptide repeat proteins (DPR)