# Treating SOD1-ALS with tofersen results in nonprogressive chronic ALS—a case series from Iceland

## TL;DR

A new treatment for a specific type of ALS shows promising results in slowing disease progression and improving motor function in patients.

## Contribution

This is the first documentation of chronic nonprogressive ALS following treatment with tofersen in patients with the SOD1 mutation.

## Key findings

- Four patients with SOD1-ALS showed no clinical deterioration after treatment with tofersen.
- Three patients demonstrated clinical improvement and some recovery of motor function.
- Neurofilament light chain levels in cerebrospinal fluid decreased to normal ranges.

## Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder. We describe four patients with hereditary ALS caused by the p.Gly94Ser SOD1 mutation who were treated monthly with the intrathecal antisense oligonucleotide tofersen in a clinical setting at Landspitali University Hospital of Iceland. After initiating treatment 15–26 months ago, no significant clinical deterioration was observed, and three patients showed signs of clinical improvement, with some recovery of motor function. All four patients currently present with chronic nonprogressive ALS, a phenotype not previously observed or documented. Concomitantly, the concentration of neurofilament light chain (Nf-L) in the cerebrospinal fluid decreased to the normal range. This clinical benefit and decrease in Nf-L levels were detected regardless of the patient’s initial ALSFRS-R score. No serious adverse events were observed. Notably, we observed a clinically meaningful effect in two patients who had been ill for several years before treatment was instituted, raising questions about who should receive treatment and the biology of paresis and motor neuron cell loss in patients with ALS. Although only a minority of ALS patients carry a SOD1 mutation, the advent of this new precision medicine has profound implications for ALS management.

The online version contains supplementary material available at 10.1007/s00415-025-13579-y.