PUBLICATION
Efficacy of Ciprofloxacin/Celecoxib combination in zebrafish models of amyotrophic lateral sclerosis
- Authors
- Goldshtein, H., Muhire, A., Petel Légaré, V., Pushett, A., Rotkopf, R., Shefner, J.M., Peterson, R.T., Armstrong, G.A.B., Russek-Blum, N.
- ID
- ZDB-PUB-201002-23
- Date
- 2020
- Source
- Annals of clinical and translational neurology 7(10): 1883-1897 (Journal)
- Registered Authors
- Peterson, Randall, Russek-Blum, Niva
- Keywords
- none
- MeSH Terms
-
- Amyotrophic Lateral Sclerosis/drug therapy*
- Amyotrophic Lateral Sclerosis/genetics
- Animals
- Animals, Genetically Modified
- Celecoxib/pharmacology*
- Ciprofloxacin/pharmacology*
- DNA-Binding Proteins/genetics
- Disease Models, Animal
- Motor Neurons/drug effects*
- Mutation/genetics
- Neuromuscular Junction/drug effects
- Superoxide Dismutase/genetics
- Zebrafish/genetics
- Zebrafish Proteins/genetics
- PubMed
- 32915525 Full text @ Ann Clin Transl Neurol
Citation
Goldshtein, H., Muhire, A., Petel Légaré, V., Pushett, A., Rotkopf, R., Shefner, J.M., Peterson, R.T., Armstrong, G.A.B., Russek-Blum, N. (2020) Efficacy of Ciprofloxacin/Celecoxib combination in zebrafish models of amyotrophic lateral sclerosis. Annals of clinical and translational neurology. 7(10):1883-1897.
Abstract
Objective To evaluate the efficacy of a fixed-dose combination of two approved drugs, Ciprofloxacin and Celecoxib, as a potential therapeutic treatment for amyotrophic lateral sclerosis (ALS).
Methods Toxicity and efficacy of Ciprofloxacin and Celecoxib were tested, each alone and in distinct ratio combinations in SOD1 G93R transgenic zebrafish model for ALS. Quantification of swimming measures following stimuli, measurements of axonal projections from the spinal cord, neuromuscular junction structure and morphometric analysis of microglia cells were performed in the combination- treated vs nontreated mutant larvae. Additionally, quantifications of touch-evoked locomotor escape response were conducted in treated vs nontreated zebrafish expressing the TARDBP G348C ALS variant.
Results When administered individually, Ciprofloxacin had a mild effect and Celecoxib had no therapeutic effect. However, combined Ciprofloxacin and Celecoxib (Cipro/Celecox) treatment caused a significant increase of ~ 84% in the distance the SOD1 G93R transgenic larvae swam. Additionally, Cipro/Celecox elicited recovery of impaired motor neurons morphology and abnormal neuromuscular junction structure and preserved the ramified morphology of microglia cells in the SOD1 mutants. Furthermore, larvae expressing the TDP-43 mutation displayed evoked touch responses that were significantly longer in swim distance (110% increase) and significantly higher in maximal swim velocity (~44% increase) when treated with Cipro/Celecox combination.
Interpretation Cipro/Celecox combination improved locomotor and cellular deficits of ALS zebrafish models. These results identify this novel combination as effective, and may prove promising for the treatment of ALS.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping