Ten years after the “Ice Bucket Challenge”, research shows progress in the treatment of amyotrophic lateral sclerosis (ALS). Certain genetic forms of the disease can now be controlled with medication, although functional limitations are partially reversible. The German Society of Neurology (DGN) is drawing attention to this at its Congress 2025 in Berlin, which runs until 15 November. According to the DGN, this indicates that less irreversible nerve damage occurs than previously thought, which raises hope for neurodegenerative diseases.

Antisense oligonucleotides (ASOs) such as tofersen, which blocks the production of harmful proteins in SOD1 mutations, led to a decline in the biomarker neurofilament light chain (NfL) in 58 percent of those affected in a study with 16 patients. 60 percent reported clinical improvements. In FUS mutations, the ASO Jacifusen showed a NfL reduction of up to 82.8 percent in a case series, with functional recovery in patients with low symptom burden.

A new monoclonal antibody (AP-101) against misfolded SOD1 proteins showed promising results in a Phase 2 study in sporadic and SOD1-ALS, including stabilized disease stages and improved survival. Therapy as an infusion is simpler than intrathecal ASO injections. A larger phase 3 study is expected to confirm the results.

A new biological classification of ALS enables more precise study designs to develop targeted therapies for subtypes. Experts see this as the basis for further progress, with the long-term goal of making ALS curable.

Original Papers:

[1] Meyer T, Schumann P, Weydt P et al. Clinical and patient-reported outcomes and neurofilament response during tofersen treatment in SOD1-related ALS-A multicenter observational study over 18 months. Muscle Nerve. 2024 Sep; 70(3):333-345.
[2] Shneider NA, Harms MB, Korobeynikov VA e al. Antisense oligonucleotide jacifusen for FUS-ALS: an investigator-initiated, multicentre, open-label case series. Lancet. 2025 May 22:S0140-6736(25)00513-6.
[3] https://www.neurimmune.com/news/al-s-pharma-announces-positive-topline-results-from-phase-2-study-of-ap-101-for-the-treatment-of-amyotrophic-lateral-sclerosis-als
[4] Meyer T, Boentert M, Großkreutz J et al. Motor phenotypes of amyotrophic lateral sclerosis – a three-determinant anatomical classification based on the region of onset, propagation of motor symptoms, and the degree of upper and lower motor neuron dysfunction. Neurol Res Pract. 2025 Apr 28; 7(1):27.

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