Neurol. praxi. 2026;27(2):125-129 | DOI: 10.36290/neu.2025.084

Targeted silencing: antisense oligonucleotides and genetic forms ALS

MUDr. Daniel Baumgartner, Ph.D.¹, MUDr. Adam Betík², doc. MUDr. Eva Vlčková, Ph.D.²

¹ Neurologická klinika 2. LF UK a FN Motol, Praha

² Neurologická klinika LF MU a FN Brno, Neuromuskulární centrum ERN, Brno

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder with limited therapeutic options. Tofersen, an antisense oligonucleotide targeting SOD1 mutations, represents the first approved gene therapy for ALS. Clinical studies demonstrated a significant biological effect through reduction of SOD1 protein and neurofilament levels, although short-term clinical benefit was not consistently confirmed. Long-term and real-world data suggest slowed disease progression, particularly when treatment is initiated early. Despite the occurrence of adverse events, the overall benefitrisk balance is considered favorable, as reflected by conditional approval in the USA and EU. We also have roughly one year of experience with the treatment in the Czech Republic as part of the compassionate use program.

Keywords: amyotrophic lateral sclerosis (ALS), SOD1 mutations, genetic therapy, antisense oligonucleotides (ASO), tofersen, neurofilaments.

Received: December 14, 2025; Revised: December 14, 2025; Accepted: December 16, 2025; Prepublished online: December 16, 2025; Published: April 29, 2026  Show citation