Journal Article

FZJ-2023-02035

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Oral Treatment with d-RD2RD2 Impedes Early Disease Mechanisms in SOD1*G93A Transgenic Mice but Does Not Prolong Survival

Wintz, K.FZJ* ; Post, J. ; Langen, K.-J.FZJ* ; Willbold, D.FZJ* ; Willuweit, A. (Corresponding author)FZJ* ; Kutzsche, J. (Corresponding author)FZJ*

2023
MDPI Basel

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Please use a persistent id in citations: http://hdl.handle.net/2128/34445  doi:10.3390/biomedicines11040995

Abstract: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting upper and lower motor neurons, thus, progressing to complete muscle loss until the patient dies from respiratory arrest. The disease is not curable, and patients die approximately 2–5 years after diagnosis. Studying the underlying disease mechanisms to get access to new treatment options is, therefore, essential for patients’ benefit. However, so far, only three drugs that alleviate the symptoms have been approved by the U.S. Food and Drug Administration (FDA). A new drug candidate for the treatment of ALS is the all-d-enantiomeric peptide RD2RD2. In this study, we investigated the therapeutic effect of RD2RD2 in two setups. First, we analyzed disease progression and survival in 7 week-old B6.Cg-Tg(SOD1*G93A)1Gur/J mice. Second, we confirmed the result of the survival analysis in the B6SJL-Tg(SOD1*G93A)1Gur/J mouse line. Shortly before disease onset, the mice were treated daily with an oral dose of 50 mg/kg body weight. Treatment with RD2RD2 led to a delayed disease onset and reduced motor phenotype as shown using the SHIRPA test, the splay reflex test, and the pole test, but did not affect survival. In conclusion, RD2RD2 has the ability to delay the onset of symptoms.

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Contributing Institute(s):

1. Strukturbiochemie (IBI-7)
2. Physik der Medizinischen Bildgebung (INM-4)

Research Program(s):

1. 5244 - Information Processing in Neuronal Networks (POF4-524) (POF4-524)

Appears in the scientific report 2023

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