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Post, J.* ; Schaffrath, A.* ; Gering, I.* ; Hartwig, S.* ; Lerch, S.* ; Shah, N.J.* ; Langen, K.J.* ; Willbold, D.* ; Kutzsche, J.* ; Willuweit, A.*

Oral treatment with RD2RD2 impedes development of motoric phenotype and delays symptom onset in SOD1G93A transgenic mice.

Int. J. Mol. Sci. 22:7066 (2021)
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Neuroinflammation is a pathological hallmark of several neurodegenerative disorders and plays a key role in the pathogenesis of amyotrophic lateral sclerosis (ALS). It has been implicated as driver of disease progression and is observed in ALS patients, as well as in the transgenic SOD1G93A mouse model. Here, we explore and validate the therapeutic potential of the d-enantiomeric peptide RD2RD2 upon oral administration in SOD1G93A mice. Transgenic mice were treated daily with RD2RD2 or placebo for 10 weeks and phenotype progression was followed with several behavioural tests. At the end of the study, plasma cytokine levels and glia cell markers in brain and spinal cord were analysed. Treatment resulted in a significantly increased performance in behavioural and motor coordination tests and a decelerated neurodegenerative phenotype in RD2RD2-treated SOD1G93A mice. Additionally, we observed retardation of the average disease onset. Treatment of SOD1G93A mice led to significant reduction in glial cell activation and a rescue of neurons. Analysis of plasma revealed normalisation of several cytokines in samples of RD2RD2-treated SOD1G93A mice towards the levels of non-transgenic mice. In conclusion, these findings qualify RD2RD2 to be considered for further development and testing towards a disease modifying ALS treatment.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Sod1g93a ; Amyotrophic Lateral Sclerosis ; Behaviour ; D-enantiomeric Peptide ; Motor Coordination ; Neuroinflammation ; Plasma Cytokines
Language english
Publication Year 2021
HGF-reported in Year 2021
ISSN (print) / ISBN 1661-6596
e-ISSN 1422-0067
Journal International Journal of Molecular Sciences
Quellenangaben Volume: 22, Issue: 13, Pages: , Article Number: 7066 Supplement: ,
Publisher MDPI
Publishing Place Basel
Reviewing status Peer reviewed
Institute(s) Helmholtz AI - FZJ (HAI - FZJ)
Grants Impuls und Vernetzungs-Fonds der Helmholtzgemeinschaft
Forschungszentrum Jülich
DOI 10.3390/ijms22137066
PubMed ID 34209129
Erfassungsdatum 2021-07-28
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