tadnersen

Tadnersen is an antisense oligonucleotide designed to selectively reduce mutant C9orf72 sense transcripts associated with C9orf72 hexanucleotide repeat expansion amyotrophic lateral sclerosis (ALS), thereby decreasing the production of toxic RNA species and dipeptide repeat proteins that drive neurodegeneration.[1][3][4][5][6] It is a thiolated ASO that binds to a site in intron 1 adjacent to the 5′ end of sense RNA transcribed from the mutant C9orf72 gene, leading to RNase H–mediated degradation of the targeted transcripts and preferential knockdown of expansion-carrying C9ORF72 variants 1 and 3 while largely sparing normal alleles.[3][4][5][6] Tadnersen was co-developed by Ionis Pharmaceuticals and Biogen for intrathecal administration in C9orf72-associated ALS, but clinical development was discontinued after a phase 1 program showed no evidence of clinical benefit despite target engagement.[1][5][6]

Other names

tadnersen sodium