Journal Article (Review Article)

DZNE-2025-00233

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Tofersen and other antisense oligonucleotides in ALS.

Ludolph, A. (First author)DZNE* ; Wiesenfarth, M.

2025
Sage London [u.a.]

This record in other databases:    

Please use a persistent id in citations: doi:10.1177/17562864251313915

Abstract: The advent of antisense oligonucleotide (ASO) therapies in neurodegenerative disorders is associated with enormous hope. Nusinersen treatment was a breakthrough intervention in the recessive disease spinal muscular atrophy, and superoxide dismutase 1 (SOD1) amyotrophic lateral sclerosis (ALS) seems to be the paradigm disease in dominant degenerative diseases. The results of treatment with the ASO tofersen in SOD1-ALS show that the drug has a convincing beneficial effect on ALS caused by SOD1 mutations, that preclinical studies in rodents predicted the therapeutic effect in the human disease, and that clinical efficacy is associated with a specific sequence of effects of the drug on mechanistic and degenerative biomarkers and, subsequently, functional outcomes such as weight stabilization and ALSFRS-R. Therefore, the enthusiasm seems to be justified; but this should be followed by an attempt to obtain further insights with the goal to improve this therapy. In particular, the following issues are only partially resolved: Which mechanisms are responsible for the clinical effect following the downregulation of SOD1 protein by ASOs? Is long-term downregulation of SOD1 function associated with side effects? Is there an autoimmune response caused by this and other ASO? Is prevention of SOD1-associated ALS possible?

Keyword(s): amyotrophic lateral sclerosis ; antisense oligonucleotides ; superoxide dismutase ; tofersen

---

Contributing Institute(s):

1. Clinical Study Center (Ulm) (Clinical Study Center (Ulm))

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2025

---

Database coverage:
; ; ; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; National-Konsortium ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---