Efficacy of Ciprofloxacin/Celecoxib combination in zebrafish models of amyotrophic lateral sclerosis

Goldshtein, Hagit; Muhire, Alexandre; Légaré, Virginie Petel; Pushett, Avital; Rotkopf, Ron; Shefner, Jeremy M.; Peterson, Randall T.; Armstrong, Gary A. B.; Blum, Niva Russek‐

doi:10.1002/acn3.51174

Cited by 18 publications

(12 citation statements)

References 60 publications

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“…Ciprofloxacin is an approved synthetic antibiotic and celecoxib is an approved nonsteroidal anti-inflammatory drug. Combination treatment improved zebrafish larvae performance and motor neuron axonopathy, and recovered the ramified morphology of microglia and NMJ structures (Goldshtein et al, 2020). These results provide a novel view of drug combination as an effective and promising treatment for ALS.…”

Section: Drug Discovery In Zebrafish Models Of Amyotrophic Lateral Sclerosismentioning

confidence: 68%

Advances of Zebrafish in Neurodegenerative Disease: From Models to Drug Discovery

Wang

Zhang

et al. 2021

Front. Pharmacol.

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Neurodegenerative disease (NDD), including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, are characterized by the progressive loss of neurons which leads to the decline of motor and/or cognitive function. Currently, the prevalence of NDD is rapidly increasing in the aging population. However, valid drugs or treatment for NDD are still lacking. The clinical heterogeneity and complex pathogenesis of NDD pose a great challenge for the development of disease-modifying therapies. Numerous animal models have been generated to mimic the pathological conditions of these diseases for drug discovery. Among them, zebrafish (Danio rerio) models are progressively emerging and becoming a powerful tool for in vivo study of NDD. Extensive use of zebrafish in pharmacology research or drug screening is due to the high conserved evolution and 87% homology to humans. In this review, we summarize the zebrafish models used in NDD studies, and highlight the recent findings on pharmacological targets for NDD treatment. As high-throughput platforms in zebrafish research have rapidly developed in recent years, we also discuss the application prospects of these new technologies in future NDD research.

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Section: Drug Discovery In Zebrafish Models Of Amyotrophic Lateral Sclerosismentioning

confidence: 68%

Advances of Zebrafish in Neurodegenerative Disease: From Models to Drug Discovery

Wang

Zhang

et al. 2021

Front. Pharmacol.

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“…Targeting of multiple ALS pathways can potentially be achieved by administration of drug combinations. In this direction, a combination of ciprofloxacin and celecoxib resulted in significant improvement of motor activity as assessed by swimming distance and velocity in Tg‐ SOD1 G93R zebrafish and in zebrafish generated after injection of an mRNA encoding for TDP‐43 G348C in one‐cell zygote 197 . A clinical trial to assess the efficacy of this drug combination in ALS has been initiated (NCT04090684).…”

Section: Design Of New Clinical Trialsmentioning

confidence: 99%

A chemogenomic approach is required for effective treatment of amyotrophic lateral sclerosis

Pampalakis

Angelis

Zingkou

et al. 2022

Clinical & Translational Med

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ALS is a fatal untreatable disease involving degeneration of motor neurons. Μultiple causative genes encoding proteins with versatile functions have been identified indicating that diverse biological pathways lead to ALS. Chemical entities still represent a promising choice to delay ALS progression, attenuate symptoms and/or increase life expectancy, but also gene‐based and stem cell‐based therapies are in the process of development, and some are tested in clinical trials. Various compounds proved effective in transgenic models overexpressing distinct ALS causative genes unfortunately though, they showed no efficacy in clinical trials. Notably, while animal models provide a uniform genetic background for preclinical testing, ALS patients are not stratified, and the distinct genetic forms of ALS are treated as one group, which could explain the observed discrepancies between treating genetically homogeneous mice and quite heterogeneous patient cohorts. We suggest that chemical entity‐genotype correlation should be exploited to guide patient stratification for pharmacotherapy, that is administered drugs should be selected based on the ALS genetic background.

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“…To conclude, these zebrafish ALS models are complementary to the existing mammal ones. Transgenic zebrafishes are often used in in-vitro and in-vivo studies for the development of new therapeutics [286][287][288].…”

Section: Zebrafish Carrying Cu/zn Sod1 Mutationsmentioning

confidence: 99%

Nearly 30 Years of Animal Models to Study Amyotrophic Lateral Sclerosis: A Historical Overview and Future Perspectives

Bonifacino

Zerbo

Balbi

et al. 2021

IJMS

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Amyotrophic lateral sclerosis (ALS) is a fatal, multigenic, multifactorial, and non-cell autonomous neurodegenerative disease characterized by upper and lower motor neuron loss. Several genetic mutations lead to ALS development and many emerging gene mutations have been discovered in recent years. Over the decades since 1990, several animal models have been generated to study ALS pathology including both vertebrates and invertebrates such as yeast, worms, flies, zebrafish, mice, rats, guinea pigs, dogs, and non-human primates. Although these models show different peculiarities, they are all useful and complementary to dissect the pathological mechanisms at the basis of motor neuron degeneration and ALS progression, thus contributing to the development of new promising therapeutics. In this review, we describe the up to date and available ALS genetic animal models, classified by the different genetic mutations and divided per species, pointing out their features in modeling, the onset and progression of the pathology, as well as their specific pathological hallmarks. Moreover, we highlight similarities, differences, advantages, and limitations, aimed at helping the researcher to select the most appropriate experimental animal model, when designing a preclinical ALS study.

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Efficacy of Ciprofloxacin/Celecoxib combination in zebrafish models of amyotrophic lateral sclerosis

Cited by 18 publications

References 60 publications

Advances of Zebrafish in Neurodegenerative Disease: From Models to Drug Discovery

Advances of Zebrafish in Neurodegenerative Disease: From Models to Drug Discovery

A chemogenomic approach is required for effective treatment of amyotrophic lateral sclerosis

Nearly 30 Years of Animal Models to Study Amyotrophic Lateral Sclerosis: A Historical Overview and Future Perspectives

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