Therapeutic strategies for C9orf72 amyotrophic lateral sclerosis and frontotemporal dementia.

ABSTRACT:

Purpose of review

An intronic G4C2 expansion mutation in C9orf72 is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD). Although there are currently no treatments for this insidious, fatal disease, intense research has led to promising therapeutic strategies, which will be discussed here.

Recent findings

Therapeutic strategies for C9-ALS/FTD have primarily focused on reducing the toxic effects of mutant expansion RNAs or the dipeptide repeat proteins (DPRs). The pathogenic effects of G4C2 expansion transcripts have been targeted using approaches aimed at promoting their degradation, inhibiting nuclear export or silencing transcription. Other promising strategies include immunotherapy to reduce the DPRs themselves, reducing

SUBMITTER: Hautbergue GM 

PROVIDER: S-EPMC8678157 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature