Electromagnetic Modulation of the ALS Transcriptome: Toward a Non-Drug Therapeutic Strategy
12 affiliations
- 1Dresden High Magnetic Field Laboratory (HLD), Helmholtz-Zentrum Dresden-Rossendorf, 01328 Dresden, Germany
- 2Division for Neurodegenerative Disease, Department Neurology, Technische Universität Dresden, 01307 Dresden, Germany
- 3Translational Neurodegeneration Section “Albrecht-Kossel”, Department of Neurology, University Medical Center Rostock, University of Rostock, 18147 Rostock, Germany
- 4Department of Radiopharmaceutical and Chemical Biology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, 01328 Dresden, Germany
- 5Faculty of Chemistry and Food Chemistry, School of Science, Technische Universität Dresden, 01069 Dresden, Germany
- 6Institute of Solid State and Materials Physics, Technische Universität Dresden, 01307 Dresden, Germany
- 7DRESDEN-concept Genome Center (DcGC), Center for Molecular and Cellular Bioengineering (CMCB) Technology Platform, TUD Dresden University of Technology, 01062 Dresden, Germany
- 8Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany
- 9German Center for Neurodegenerative Diseases (DZNE) Rostock/Greifswald, 18147 Rostock, Germany
- 10Center for Transdisciplinary Neurosciences Rostock (CTNR), University Medical Center Rostock, University of Rostock, 18147 Rostock, Germany
- 11Institute of Anatomy, Medizinisch Theoretisches Zentrum, Technische Universität Dresden, 01307 Dresden, Germany
- 12Dresden International University, 01067 Dresden, Germany
Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease hallmarked by progressive loss of neuromuscular junctions, cortical and spinal motor neurons (MNs), resulting in muscle paralysis. MNs are particularly vulnerable due to their long axons and high metabolic demands. ALS pathology involves impaired RNA metabolism, protein aggregation, cytoskeletal defects affecting organelle trafficking, and mitochondrial dysfunction, ultimately leading to neurodegeneration. Current treatments only marginally extend survival, calling for alternative therapies. We recently reported beneficial effects of electromagnetic alternating field stimulation (ACMS) on axonal regeneration and organelle motility in ALS. Here, we used iPSC-derived spinal MNs from familial ALS patients with FUS mutations to optimize magnetic field parameters regarding frequency, amplitude and duration. Using compartmentalized neuron cultures, we also tested different magnetic field orientations relative to axons. Following ACMS, we assessed axonal organelle trafficking and the nuclear DNA damage response (DDR) by live-cell imaging. Untreated ALS neurons showed clear defects in both assays. Exposure to magnetic AC sine waves above a threshold amplitude of 7 mT, applied perpendicular to the axonal plane with an optimal low frequency of 25 Hz, led to a sustained boost of mitochondrial and lysosomal motility for over one week and rehabilitation of DDR. These phenotypic improvements correlated with global transcriptomic changes revealed by RNA-sequencing. These phenotypic improvements correlated with global transcriptomic changes revealed by RNA-sequencing. While untreated mutant and wild-type neurons displayed different gene expression profiles, ACMS converged them to a novel, harmonized transcriptional state across all lines. Further analysis of differentially expressed genes (DEGs) yielded a conceptual model in which ACMS activates extracellular matrix (ECM)-mediated cell adhesion and neurotransmitter receptor, ion channel and kinase signaling pathways, ultimately modulating gene transcription and, thereby, motor- and microtubule-associated proteins. This model provides a framework for follow-up studies to experimentally validate the underlying mechanisms and assess the therapeutic potential of ACMS as an alternative biophysical treatment modality for neurodegenerative diseases.
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BibTeX
@article{pal2026electromagnetic,
title = {{Electromagnetic Modulation of the ALS Transcriptome: Toward a Non-Drug Therapeutic Strategy}},
author = {Arun Pal and Banaja P. Dash and Marc Uhlarz and Jonas Gronemann and Julia Japtok and Hannes Glaß and Jens Pietzsch and Joachim Wosnitza and Katrin Sameith and Andreas Dahl and Andreas Hermann and Richard H. W. Funk and Thomas Herrmannsdörfer},
journal = {Cells},
year = {2026},
month = nov,
doi = {10.3390/cells15212003},
url = {https://www.mdpi.com/2073-4409/15/21/2003},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Electromagnetic Modulation of the ALS Transcriptome: Toward a Non-Drug Therapeutic Strategy
AU - Arun Pal
AU - Banaja P. Dash
AU - Marc Uhlarz
AU - Jonas Gronemann
AU - Julia Japtok
AU - Hannes Glaß
AU - Jens Pietzsch
AU - Joachim Wosnitza
AU - Katrin Sameith
AU - Andreas Dahl
AU - Andreas Hermann
AU - Richard H. W. Funk
AU - Thomas Herrmannsdörfer
PY - 2026
DA - 2026/11/03
JO - Cells
DO - 10.3390/cells15212003
UR - https://www.mdpi.com/2073-4409/15/21/2003
AB - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease hallmarked by progressive loss of neuromuscular junctions, cortical and spinal motor neurons (MNs), resulting in muscle paralysis. MNs are particularly vulnerable due to their long axons and high metabolic demands. ALS pathology involves impaired RNA metabolism, protein aggregation, cytoskeletal defects affecting organelle trafficking, and mitochondrial dysfunction, ultimately leading to neurodegeneration. Current treatments only marginally extend survival, calling for alternative therapies. We recently reported beneficial effects of electromagnetic alternating field stimulation (ACMS) on axonal regeneration and organelle motility in ALS. Here, we used iPSC-derived spinal MNs from familial ALS patients with FUS mutations to optimize magnetic field parameters regarding frequency, amplitude and duration. Using compartmentalized neuron cultures, we also tested different magnetic field orientations relative to axons. Following ACMS, we assessed axonal organelle trafficking and the nuclear DNA damage response (DDR) by live-cell imaging. Untreated ALS neurons showed clear defects in both assays. Exposure to magnetic AC sine waves above a threshold amplitude of 7 mT, applied perpendicular to the axonal plane with an optimal low frequency of 25 Hz, led to a sustained boost of mitochondrial and lysosomal motility for over one week and rehabilitation of DDR. These phenotypic improvements correlated with global transcriptomic changes revealed by RNA-sequencing. These phenotypic improvements correlated with global transcriptomic changes revealed by RNA-sequencing. While untreated mutant and wild-type neurons displayed different gene expression profiles, ACMS converged them to a novel, harmonized transcriptional state across all lines. Further analysis of differentially expressed genes (DEGs) yielded a conceptual model in which ACMS activates extracellular matrix (ECM)-mediated cell adhesion and neurotransmitter receptor, ion channel and kinase signaling pathways, ultimately modulating gene transcription and, thereby, motor- and microtubule-associated proteins. This model provides a framework for follow-up studies to experimentally validate the underlying mechanisms and assess the therapeutic potential of ACMS as an alternative biophysical treatment modality for neurodegenerative diseases.
SN - 2073-4409
ER -