ORIGINAL RESEARCH article
Front. Neurol.
Sec. Experimental Therapeutics
Volume 16 - 2025 | doi: 10.3389/fneur.2025.1594169
Multi-Path Direct Current Spinal Stimulation Extended Survival in The SOD1-G93A Model of Amyotrophic Lateral Sclerosis
Provisionally accepted
- 1College of Staten Island, Staten Island, United States
- 2Department of Physical Therapy, College of Staten Island, Staten Island, New York, United States
- 3The Graduate Center,The City University of New York, New York City, New York, United States
- 4Brooklyn College (CUNY), Brooklyn, New York, United States
- 5Helene Fuld College of Nursing, New York City, New York, United States
- 6York College, City University of New York, New York City, New York, United States
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Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons in the spinal cord and brain. We have developed a novel non-invasive approach, MultiPath-DCS, that utilizes direct current stimulation at multiple sites along the neural axis and applies simultaneous spinal and peripheral stimulation targeted to the affected limbs. MultiPath-DCS modulates spinal cord neuronal excitability. This effect of MultiPath-DCS is relevant to ALS as motor neuron hyperexcitability is a fundamental characteristic of the disease. Using a transgenic mouse model of ALS (SOD1-G93A), we have demonstrated molecular changes induced by anodal MultiPath DCS, including (a) reduced expression of mutant SOD1 protein, (b) reduced expression of elevated NKCC1, (c) reduced phosphorylated tau, (d) increased expression of HSP70, and (e) increased expression of LC3B. Additionally, we found that treatment with Anodal-MultiPath-DCS (anode on the spinal column) reduces neuronal spinal excitability long-term, slows the progression of muscle weakness, and increases the life span of stimulated mice. The mean survival time in the control group was 12.4 days. In comparison, the mean survival time in the stimulated group was 21.6 days using a therapeutic stimulation paradigm, representing 74% increased survival from disease onset. Spinal motor neuron survival counts showed a 54% increase in stimulated compared to non-stimulated groups. Together, these data provide evidence that Anodal-MultiPath-DCS reduces hyperexcitability and enhances the clearance of misfolded proteins by modulating autophagy and proteolytic systems. By reducing spinal excitability and clearing toxic proteins from motor neurons, Anodal-MultiPath-DCS promotes survival and could become a disease-modifying intervention for ALS.
Keywords: ALS (Amyotrophic lateral sclerosis), Direct current stimulation (tDCS), spinal motor neuron, Survival, Neuroprotection
Received: 15 Mar 2025; Accepted: 19 May 2025.
Copyright: © 2025 Ahmed, Samaddar, Hassieb, Sadek, Morozova and Begum. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Zaghloul Ahmed, College of Staten Island, Staten Island, United States
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