Failure of <i>C9orf72</i> sense repeat-targeting antisense oligonucleotides: lessons learned and the path forward-Reference-Cited by-同舟云学术

Failure of C9orf72 sense repeat-targeting antisense oligonucleotides: lessons learned and the path forward

Published:2024-05-29 Issue:8 Volume:147 Page:2607-2609
ISSN:0006-8950
Container-title:Brain
language:en
Short-container-title:

Author:

Cammack Alexander J¹²,Balendra Rubika¹²,Isaacs Adrian M¹²^ORCID

Affiliation:

1. UK Dementia Research Institute at UCL , London, WC1E 6BT , UK

2. Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology , London, WC1N 3BG , UK

Abstract

The recent failure of two independent clinical trials targeting C9orf72 sense repeat-containing RNAs with antisense oligonucleotides was a great disappointment for the field. Cammack et al. discuss the data from these trials, possible reasons for the failures, and the future of C9orf72 therapeutic targeting moving forward.

Funder

Live Like Lou

Academy of Medical Sciences Starter

Clinical Lecturers

UK Dementia Research Institute

Medical Research Council

LifeArc

Alzheimer’s Research UK

Publisher

Oxford University Press (OUP)

Link

https://academic.oup.com/brain/advance-article-pdf/doi/10.1093/brain/awae168/58476575/awae168.pdf

Reference10 articles.

1. C9orf72-mediated ALS and FTD: Multiple pathways to disease;Balendra;Nat Rev Neurol,2018

2. Gain of toxicity from ALS/FTD-linked repeat expansions in C9ORF72 is alleviated by antisense oligonucleotides targeting GGGGCC-containing RNAs;Jiang;Neuron,2016

3. Variant-selective stereopure oligonucleotides protect against pathologies associated with C9orf72-repeat expansion in preclinical models;Liu;Nat Commun,2021

4. Results from the phase 1 trial and open label extension evaluating BIIB078 in adults with C9orf72-ALS;Van Den Berg;ENCALS Meeting,2022

5. Suppression of mutant C9orf72 expression by a potent mixed backbone antisense oligonucleotide;Tran;Nat Med,2022