Real-world tofersen lowers neurofilaments in SOD1-ALS
In 24 German early-access SOD1-ALS patients, tofersen slowed ALSFRS-R decline versus pre-treatment and cut serum NfL and CSF pNfH, but CSF pleocytosis was common.
Source
Effects of tofersen treatment in patients with SOD1-ALS in a "real-world" setting - a 12-month multicenter cohort study from the German early access program
Study at a glance
- Design
- Other — Prospective observational follow-up in Germany’s tofersen early-access program across ten MND-NET centres
- N
- N=24 · SOD1-ALS patients treated March 2022–April 2023
- Population
- Adults with SOD1-ALS in a German early-access programme
- Outcome
- ALSFRS-R progression and serum/CSF neurofilament change on tofersen
Structured fields used in claim comparison tables when every cited study has a complete layer.
What they did
Investigators followed 24 SOD1-ALS patients treated via Germany’s tofersen early access program (March 2022–April 2023) across ten MND-NET centers. They tracked ALSFRS-R, progression rate, quality of life, serum NfL, CSF pNfH, CSF inflammatory markers, and adverse events using a uniform protocol and central CSF/blood assays.
What they found
Median ALSFRS-R decreased from 38.0 to 35.0 (progression 0.11 points/month), slower than pre-baseline progression (0.41 points/month; p = 0.04 in subset). Serum NfL and CSF pNfH each fell significantly (p = 0.02). No deaths occurred, but pleocytosis appeared in 73% and intrathecal immunoglobulin synthesis in 90%; two drug-related serious adverse events included autoimmune myeloradiculitis requiring immunotherapy.
The limits
What it doesn't show
There was no placebo control, sample size was small, follow-up was short and heterogeneous, and pre-baseline slopes relied on recall—so clinical benefit beyond biomarker change remains uncertain and placebo effects cannot be excluded.
Key terms
- Tofersen
- Antisense oligonucleotide given intrathecally to reduce SOD1 protein by degrading its mRNA.
- SOD1-ALS
- Amyotrophic lateral sclerosis caused by pathogenic variants in the superoxide dismutase 1 gene.
- Neurofilament light chain (NfL)
- Blood biomarker of axonal injury that fell during tofersen treatment.
- pNfH
- Phosphorylated neurofilament heavy chain measured in CSF as a marker of neurodegeneration.
- ALSFRS-R
- 12-item functional rating scale for ALS disability used to compute monthly progression rate.
- Pleocytosis
- Elevated CSF white cells, here often asymptomatic but suggesting CNS immune activation.
Flashcards
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Quiz yourself
How many patients were included?
Common questions
Did neurofilament levels improve on tofersen?
Yes—median serum NfL and CSF pNfH both declined significantly over treatment (p = 0.02).
Was functional decline slower than before treatment?
Median on-treatment ALSFRS-R loss (0.11 points/month) was lower than pre-baseline progression (0.41) in the analyzable subset.
Was treatment safe in this cohort?
No deaths occurred, but CSF inflammation was common and two serious drug-related events included autoimmune myeloradiculitis.
How does this relate to the VALOR trial?
It corroborates VALOR/OLE NfL reductions and extends evidence to pNfH in CSF in a less selected real-world cohort.
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