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A zebrafish drug screening platform boosts the discovery of novel therapeutics for spinal cord injury in mammals

Spinal cord injury (SCI) is a complex condition, with limited therapeutic options, that results in sensory and motor disabilities. To boost discovery of novel therapeutics, we designed a simple and efficient drug screening platform. This innovative approach allows to determine locomotor rescue prope...

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Autores principales: Chapela, Diana, Sousa, Sara, Martins, Isaura, Cristóvão, Ana Margarida, Pinto, Patrícia, Corte-Real, Sofia, Saúde, Leonor
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6642202/
https://www.ncbi.nlm.nih.gov/pubmed/31324865
http://dx.doi.org/10.1038/s41598-019-47006-w
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author Chapela, Diana
Sousa, Sara
Martins, Isaura
Cristóvão, Ana Margarida
Pinto, Patrícia
Corte-Real, Sofia
Saúde, Leonor
author_facet Chapela, Diana
Sousa, Sara
Martins, Isaura
Cristóvão, Ana Margarida
Pinto, Patrícia
Corte-Real, Sofia
Saúde, Leonor
author_sort Chapela, Diana
collection PubMed
description Spinal cord injury (SCI) is a complex condition, with limited therapeutic options, that results in sensory and motor disabilities. To boost discovery of novel therapeutics, we designed a simple and efficient drug screening platform. This innovative approach allows to determine locomotor rescue properties of small molecules in a zebrafish (Danio rerio) larval spinal cord transection model. We validated our screening platform by showing that Riluzole and Minocycline, two molecules that are in clinical trials for SCI, promote rescue of the locomotor function of the transected larvae. Further validation of the platform was obtained through the blind identification of D-Cycloserine, a molecule scheduled to enter phase IV clinical trials for SCI. Importantly, we identified Tranexamic acid and further showed that this molecule maintains its locomotor recovery properties in a rodent female contusion model. Our screening platform, combined with drug repurposing, promises to propel the rapid translation of novel therapeutics to improve SCI recovery in humans.
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spelling pubmed-66422022019-07-25 A zebrafish drug screening platform boosts the discovery of novel therapeutics for spinal cord injury in mammals Chapela, Diana Sousa, Sara Martins, Isaura Cristóvão, Ana Margarida Pinto, Patrícia Corte-Real, Sofia Saúde, Leonor Sci Rep Article Spinal cord injury (SCI) is a complex condition, with limited therapeutic options, that results in sensory and motor disabilities. To boost discovery of novel therapeutics, we designed a simple and efficient drug screening platform. This innovative approach allows to determine locomotor rescue properties of small molecules in a zebrafish (Danio rerio) larval spinal cord transection model. We validated our screening platform by showing that Riluzole and Minocycline, two molecules that are in clinical trials for SCI, promote rescue of the locomotor function of the transected larvae. Further validation of the platform was obtained through the blind identification of D-Cycloserine, a molecule scheduled to enter phase IV clinical trials for SCI. Importantly, we identified Tranexamic acid and further showed that this molecule maintains its locomotor recovery properties in a rodent female contusion model. Our screening platform, combined with drug repurposing, promises to propel the rapid translation of novel therapeutics to improve SCI recovery in humans. Nature Publishing Group UK 2019-07-19 /pmc/articles/PMC6642202/ /pubmed/31324865 http://dx.doi.org/10.1038/s41598-019-47006-w Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Chapela, Diana
Sousa, Sara
Martins, Isaura
Cristóvão, Ana Margarida
Pinto, Patrícia
Corte-Real, Sofia
Saúde, Leonor
A zebrafish drug screening platform boosts the discovery of novel therapeutics for spinal cord injury in mammals
title A zebrafish drug screening platform boosts the discovery of novel therapeutics for spinal cord injury in mammals
title_full A zebrafish drug screening platform boosts the discovery of novel therapeutics for spinal cord injury in mammals
title_fullStr A zebrafish drug screening platform boosts the discovery of novel therapeutics for spinal cord injury in mammals
title_full_unstemmed A zebrafish drug screening platform boosts the discovery of novel therapeutics for spinal cord injury in mammals
title_short A zebrafish drug screening platform boosts the discovery of novel therapeutics for spinal cord injury in mammals
title_sort zebrafish drug screening platform boosts the discovery of novel therapeutics for spinal cord injury in mammals
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6642202/
https://www.ncbi.nlm.nih.gov/pubmed/31324865
http://dx.doi.org/10.1038/s41598-019-47006-w
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