UMMS Affiliation

Department of Pediatrics; Horae Gene Therapy Center; Department of Neurology

Publication Date


Document Type



Analytical, Diagnostic and Therapeutic Techniques and Equipment | Genetics and Genomics | Nervous System Diseases | Neuroscience and Neurobiology | Respiratory Tract Diseases


Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that results in death from respiratory failure. No cure exists for this devastating disease, but therapy that directly targets the respiratory system has the potential to prolong survival and improve quality of life in some cases of ALS. The objective of this study was to enhance breathing and prolong survival by suppressing superoxide dismutase 1 (SOD1) expression in respiratory motor neurons using adeno-associated virus (AAV) expressing an artificial microRNA targeting the SOD1 gene. AAV-miR(SOD1) was injected in the tongue and intrapleural space of SOD1(G93A) mice, and repetitive respiratory and behavioral measurements were performed until the end stage. Robust silencing of SOD1 was observed in the diaphragm and tongue as well as systemically. Silencing of SOD1 prolonged survival by approximately 50 days, and it delayed weight loss and limb weakness in treated animals compared to untreated controls. Histologically, there was preservation of the neuromuscular junctions in the diaphragm as well as the number of axons in the phrenic and hypoglossal nerves. Although SOD1 suppression improved breathing and prolonged survival, it did not ameliorate the restrictive lung phenotype. Suppression of SOD1 expression in motor neurons that underlie respiratory function prolongs survival and enhances breathing until the end stage in SOD1(G93A) ALS mice.


Amyotrophic lateral sclerosis, ALS, gene therapy

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Copyright © 2019 The Author(s). This is an open access article under the CC BY-NC-ND license (

DOI of Published Version



Mol Ther Methods Clin Dev. 2019 Dec 24;17:246-257. doi: 10.1016/j.omtm.2019.12.007. eCollection 2020 Jun 12. Link to article on publisher's site

Journal/Book/Conference Title

Molecular therapy. Methods and clinical development

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PubMed ID


Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.