A Novel Anti-Inflammatory d-Peptide Inhibits Disease Phenotype Progression in an ALS Mouse Model

Molecules, vol. 26, pp. 1590

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterised by selective neuronal death in the brain stem and spinal cord. The cause is unknown, but an increasing amount of evidence has firmly certified that neuroinflammation plays a key role in ALS pathogenesis. Neuroinflammation is a pathological hallmark of several neurodegenerative disorders and has been implicated as driver of disease progression. Here, we describe a treatment study demonstrating the therapeutic potential of a tandem version of the well-known all-d-peptide RD2 (RD2RD2) in a transgenic mouse model of ALS (SOD1*G93A). Mice were treated intraperitoneally for four weeks with RD2RD2 vs. placebo. SOD1*G93A mice were tested longitudinally during treatment in various behavioural and motor coordination tests. Brain and spinal cord samples were investigated immunohistochemically for gliosis and neurodegeneration. RD2RD2 treatment in SOD1*G93A mice resulted not only in a reduction of activated astrocytes and microglia in both the brain stem and lumbar spinal cord, but also in a rescue of neurons in the motor cortex. RD2RD2 treatment was able to slow progression of the disease phenotype, especially the motor deficits, to an extent that during the four weeks treatment duration, no significant progression was observed in any of the motor experiments. Based on the presented results, we conclude that RD2RD2 is a potential therapeutic candidate against ALS.

Authors 9

1. Julia Post

   Forschungszentrum Jülich

   Affiliation as printed

   Institute of Biological Information Processing, Structural Biochemistry, IBI-7, Forschungszentrum Jülich GmbH, 52425 Jülich, Germany

2. Vanessa Kogel

   Forschungszentrum Jülich

   Affiliation as printed

   Institute of Biological Information Processing, Structural Biochemistry, IBI-7, Forschungszentrum Jülich GmbH, 52425 Jülich, Germany

3. Anja Schaffrath

   Forschungszentrum Jülich

   Affiliation as printed

   Institute of Biological Information Processing, Structural Biochemistry, IBI-7, Forschungszentrum Jülich GmbH, 52425 Jülich, Germany

4. Philipp Lohmann

   Forschungszentrum Jülich

   Affiliation as printed

   Institute of Neuroscience and Medicine 4, INM-4, Medical Imaging Physics, Forschungszentrum Jülich GmbH, 52425 Jülich, Germany

5. Nadim Jon Shah Aachen Department of Neurology

   RWTH Aachen University · Forschungszentrum Jülich · Jülich Aachen Research Alliance

   Affiliation as printed

   Department of Neurology, RWTH Aachen University, 52062 Aachen, Germany

   Institute of Neuroscience and Medicine 11, INM-11, JARA, Forschungszentrum Jülich GmbH, 52425 Jülich, Germany

   Institute of Neuroscience and Medicine 4, INM-4, Medical Imaging Physics, Forschungszentrum Jülich GmbH, 52425 Jülich, Germany

   JARA-Brain-Translational Medicine, 52074 Aachen, Germany

6. Karl‐Josef Langen Aachen Department of Nuclear Medicine

   RWTH Aachen University · Forschungszentrum Jülich

   Affiliation as printed

   Department of Nuclear Medicine, RWTH Aachen University, 52062 Aachen, Germany

   Institute of Neuroscience and Medicine 4, INM-4, Medical Imaging Physics, Forschungszentrum Jülich GmbH, 52425 Jülich, Germany

7. Dieter Willbold corresponding

   Forschungszentrum Jülich · Heinrich Heine University Düsseldorf

   Affiliation as printed

   Institut für Physikalische Biologie, Heinrich-Heine-Universität Düsseldorf, 40225 Düsseldorf, Germany

   Institute of Biological Information Processing, Structural Biochemistry, IBI-7, Forschungszentrum Jülich GmbH, 52425 Jülich, Germany

8. Antje Willuweit corresponding

   Forschungszentrum Jülich

   Affiliation as printed

   Institute of Neuroscience and Medicine 4, INM-4, Medical Imaging Physics, Forschungszentrum Jülich GmbH, 52425 Jülich, Germany

9. Janine Kutzsche corresponding

   Forschungszentrum Jülich

   Affiliation as printed

   Institute of Biological Information Processing, Structural Biochemistry, IBI-7, Forschungszentrum Jülich GmbH, 52425 Jülich, Germany