Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2025 Feb;12(2):311-319.
doi: 10.1002/acn3.52264. Epub 2025 Jan 9.

Tofersen treatment leads to sustained stabilization of disease in SOD1 ALS in a "real-world" setting

Sean E Smith  1 , Kelly McCoy-Gross  1 , Amber Malcolm  1 , Jeri Oranski  1 , Jesse W Markway  1 , Timothy M Miller  1 , Robert C Bucelli  1
Affiliations
Observational Study

Tofersen treatment leads to sustained stabilization of disease in SOD1 ALS in a "real-world" setting

Sean E Smith et al. Ann Clin Transl Neurol. 2025 Feb.

Abstract

Objective: Patients with amyotrophic lateral sclerosis (ALS) caused by superoxide dismutase 1 (SOD1) gene mutations (SOD1 ALS) treated with tofersen have shown slowing of disease progression, and disease stabilization with recovery of function in some patients. We report our clinical experience with treating patients with SOD1 ALS and the effects of tofersen on outcome measures.

Methods: This was a single-center observational study of patients with SOD1 ALS receiving treatment with tofersen. The effects of tofersen treatment on neurofilament levels, muscle strength, and clinical outcome measures were assessed. Several patients had outpatient neuromuscular rehabilitation in addition to tofersen treatment and we report changes in functional outcomes.

Results: Seven SOD1 ALS patients received treatment at our institution. All patients showed robust and sustained declines in serum NfL and CSF pNFH (mean change serum NfL: -57.9%; mean change CSF pNFH: -67.6%). There was apparent disease stabilization as assessed by the ALSFRS-R total score, mean change 1.1 (SD = 0.7). There was notable improvement in functional independence measured by the FIM motor score, mean change 5.13 points (SD = 3.85).

Interpretation: This study provides evidence that tofersen treatment in SOD1 ALS can lead to meaningful preservation of function and suggestions of sustained improvement in neurologic function in some patients, and strongly supports the role of neurofilaments as therapeutic biomarkers.

PubMed Disclaimer

Conflict of interest statement

TMM has licensing agreements with C2N and Ionis Pharmaceuticals, has served on an advisory board and receives material support from Biogen and Ionis Pharmaceuticals, served on advisory board for UCB Pharma, is a consultant for Cytokinetics, Disarm Therapeutics, and Bioio, and received an honorarium from Denali and Regeneron. RCB has served on advisory boards for MT Pharma and Biogen, has a consulting role with Biogen, has equity in Neuroquestions LLC, and receives a recurring annual gift from a patient's family for research on neuralgic amyotrophy. The remaining authors have no conflicts of interest to disclose.

Figures

Figure 1
Figure 1
Effect on serum NfL and CSF pNFH (N = 7). Longitudinal changes in neurofilament before and during treatment with tofersen. (A) Serum NfL; (B) CSF pNFH. CSF pNFH, CSF neurofilament heavy chain in CSF; serum NfL, serum neurofilament light chain in serum.
Figure 2
Figure 2
Clinical functional outcomes. Changes in ALSFRS‐R, HHD, FIM motor score, 10MWT, TUG, and 30‐s sit to stand. All panels reflect changes from initial assessment to the last measured value. (A) ALSFRS‐R Total Score; (B) FIM Motor Score; (C) Handheld Dynamometry Total Score; (D) 10MWT; (E) TUG; (F) 30‐s sit to stand. 10MWT, 10‐meter walk test; ALSFRS‐R, ALS Functional Rating Scale‐Revised; FIM, functional independence measure; HHD, handheld dynamometry; m/s, meters per second; TUG, timed up and go. Expected; expected ALSFRS‐R is progression rate at start of tofersen treatment × months on treatment. For figures (C) through (F) Patient 2 used front wheeled walker a rollator and left ankle foot orthosis, Patient 3 used a right ankle foot orthosis, Patient 4 used a rollator and bilateral ankle foot orthoses, and Patient 7 used a right ankle foot orthosis as needed for functional tasks.
See this image and copyright information in PMC

References

    1. Bunton‐Stasyshyn RK, Saccon RA, Fratta P, Fisher EM. SOD1 function and its implications for amyotrophic lateral sclerosis pathology: new and renascent themes. Neuroscientist. 2015;21(5):519‐529. - PubMed
    1. Miller T, Cudkowicz M, Shaw PJ, et al. Phase 1‐2 trial of antisense oligonucleotide Tofersen for SOD1 ALS. N Engl J Med. 2020;383(2):109‐119. - PubMed
    1. Miller TM, Cudkowicz ME, Genge A, et al. Trial of antisense oligonucleotide Tofersen for SOD1 ALS. N Engl J Med. 2022;387(12):1099‐1110. - PubMed
    1. Ellis CM, Simmons A, Jones DK, et al. Diffusion tensor MRI assesses corticospinal tract damage in ALS. Neurology. 1999;53(5):1051‐1058. - PubMed
    1. Kimura F, Fujimura C, Ishida S, et al. Progression rate of ALSFRS‐R at time of diagnosis predicts survival time in ALS. Neurology. 2006;66(2):265‐267. - PubMed

Publication types

LinkOut - more resources