Gene Therapy Overexpressing Neuregulin 1 Type I in Combination With Neuregulin 1 Type III Promotes Functional Improvement in the SOD1 G93AALS Mice
Mòdol Caballero, Guillem (Universitat Autònoma de Barcelona. Institut de Neurociències)
Herrando-Grabulosa, Mireia (Universitat Autònoma de Barcelona. Institut de Neurociències)
Verdés, Sergi (Universitat Autònoma de Barcelona. Institut de Neurociències)
García-Lareu, Belén (Universitat Autònoma de Barcelona. Institut de Neurociències)
Hernández, Neus (Universitat Autònoma de Barcelona. Institut de Neurociències)
Francos Quijorna, Isaac (Universitat Autònoma de Barcelona. Institut de Neurociències)
López Vales, Rubén (Universitat Autònoma de Barcelona. Institut de Neurociències)
Bosch i Merino, Assumpció (Universitat Autònoma de Barcelona. Institut de Neurociències)
Navarro, X. (Xavier) (Universitat Autònoma de Barcelona. Institut de Neurociències)

Date:	2021
Abstract:	Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting the neuromuscular system for which currently there is no effective therapy. Motoneuron (MN) degeneration involves several complex mechanisms, including surrounding glial cells and skeletal muscle contributions. Neuregulin 1 (NRG1) is a trophic factor present particularly in MNs and neuromuscular junctions. Our previous studies revealed that gene therapy overexpressing the isoform I (NRG1-I) in skeletal muscles as well as overexpressing the isoform III (NRG1-III) directly in the central nervous system are both effective in preserving MNs in the spinal cord of ALS mice, opening novel therapeutic approaches. In this study, we combined administration of both viral vectors overexpressing NRG1-I in skeletal muscles and NRG1-III in spinal cord of the SOD1G93A mice in order to obtain a synergistic effect. The results showed that the combinatorial gene therapy increased preservation of MNs and of innervated neuromuscular junctions and reduced glial reactivity in the spinal cord of the treated SOD1G93A mice. Moreover, NRG1 isoforms overexpression improved motor function of hindlimb muscles and delayed the onset of clinical disease. However, this combinatory gene therapy did not produce a synergic effect compared with single therapies, suggesting an overlap between NRG1-I and NRG1-III activated pathways and their beneficial effects.
Grants:	Ministerio de Ciencia e Innovación PID2020-116735RB-I00 Ministerio de Economía y Competitividad RD16/0011/0014
Note:	Altres ajuts: Fundació La Marato-TV3: TV3201428-10; AFM Telethon: 20289
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Amyotrophic lateral sclerosis ; Neuregulin 1 ; ErbB receptors ; Motoneuron ; Neuromuscular junction ; Spinal cord
Published in:	Frontiers in neurology, Vol. 12 (Setembre 2021) , ISSN 1664-2295

DOI: 10.3389/fneur.2021.693309
PMID: 34630277
PMID: PMC8492910

12 p, 4.5 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles