ArticleNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2019
The Novel Small Molecule TRVA242 Stabilizes Neuromuscular Junction Defects in Multiple Animal Models of Amyotrophic Lateral Sclerosis.
Article in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 34 citations in OpenAlex.
- Drug screens using the nematode Caenorhabditis elegans.Genetics · 2025Review
- Drug Screening and Validation Targeting TDP-43 Proteinopathy for Amyotrophic Lateral Sclerosis.Aging and disease · 2024Review
- Neuromuscular Junction-on-a-Chip for Amyotrophic Lateral Sclerosis Modeling.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Diving deep: zebrafish models in motor neuron degeneration research.Frontiers in neuroscience · 2024Review
- Identification of side effects of COVID-19 drug candidates on embryogenesis using an integrated zebrafish screening platform.Scientific reports · 2023Article
- Assessing Drug Administration Techniques in Zebrafish Models of Neurological Disease.International journal of molecular sciences · 2023Review
- Zebrafish as a Model Organism for Studying Pathologic Mechanisms of Neurodegenerative Diseases and other Neural Disorders.Cellular and molecular neurobiology · 2023Review
- A multilevel screening pipeline in zebrafish identifies therapeutic drugs for GAN.EMBO molecular medicine · 2023Article
- Simple models to understand complex disease: 10 years of progress fromFrontiers in neuroscience · 2023Review
- Neuromuscular Junction Dysfunction in Amyotrophic Lateral Sclerosis.Molecular neurobiology · 2022Review
- Therapeutic Targets in Amyotrophic Lateral Sclerosis: Focus on Ion Channels and Skeletal Muscle.Cells · 2022Review
- A chemogenomic approach is required for effective treatment of amyotrophic lateral sclerosis.Clinical and translational medicine · 2022Review
- Modeling neuromuscular diseases in zebrafish.Frontiers in molecular neuroscience · 2022Review
- Caenorhabditis elegans for rare disease modeling and drug discovery: strategies and strengths.Disease models & mechanisms · 2021Review
- Medium-throughput zebrafish optogenetic platform identifies deficits in subsequent neural activity following brief early exposure to cannabidiol and ΔScientific reports · 2021Article
- Zebrafish, an In Vivo Platform to Screen Drugs and Proteins for Biomedical Use.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Improving mitochondria and ER stability helps eliminate upper motor neuron degeneration that occurs due to mSOD1 toxicity and TDP-43 pathology.Clinical and translational medicine · 2021Article
- Advances of Zebrafish in Neurodegenerative Disease: From Models to Drug Discovery.Frontiers in pharmacology · 2021Review
- Organ on a Chip: A NovelFrontiers in neurology · 2021Review
- Novel small molecule TRVA242 targets neuromuscular junction in amyotrophic lateral sclerosis.Neural regeneration research · 2020Review
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative disorder in which the neuromuscular junction progressively degenerates, leading to movement difficulties, paralysis, and eventually death. ALS is currently being treated by only two FDA-approved drugs with modest efficacy in slowing disease progression. Often, the translation of preclinical findings to bedside terminates prematurely as the evaluation of potential therapeutic compounds focuses on a single study or a single animal model. To circumscribe these issues, we screened 3,765 novel small molecule derivatives of pimozide, a recently identified repurposed neuroleptic for ALS, in Caenorhabditis elegans, confirmed the hits in zebrafish and validated the most active compounds in mouse genetic models. Out of the 27 small molecules identified from the high-throughput screen in worms, 4 were found to recover locomotor defects in C. elegans and genetic zebrafish models of ALS. TRVA242 was identified as the most potent compound as it significantly improved efficiency in rescuing locomotor, motorneuron, and neuromuscular junction synaptic deficits in a C. elegans TDP-43 model and in multiple zebrafish genetic (TDP-43, SOD1, and C9ORF72) models of ALS. The actions of TRVA242 were also conserved in a mammalian model as it also stabilized neuromuscular junction deficits in a mouse SOD1 model of ALS. Compounds such as TRVA242 therefore represent new potential therapeutics for the treatment of ALS.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.