PUBLICATION
A zebrafish drug screening platform boosts the discovery of novel therapeutics for spinal cord injury in mammals
- Authors
- Chapela, D., Sousa, S., Martins, I., Cristóvão, A.M., Pinto, P., Corte-Real, S., Saúde, L.
- ID
- ZDB-PUB-190724-13
- Date
- 2019
- Source
- Scientific Reports 9: 10475 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Cycloserine/therapeutic use
- Disease Models, Animal
- Drug Discovery/methods*
- Drug Evaluation, Preclinical/methods*
- Female
- Locomotion/drug effects
- Mice
- Mice, Inbred C57BL
- Minocycline/therapeutic use
- Riluzole/therapeutic use
- Spinal Cord Injuries/drug therapy*
- Tranexamic Acid/therapeutic use
- Zebrafish/injuries*
- PubMed
- 31324865 Full text @ Sci. Rep.
Citation
Chapela, D., Sousa, S., Martins, I., Cristóvão, A.M., Pinto, P., Corte-Real, S., Saúde, L. (2019) A zebrafish drug screening platform boosts the discovery of novel therapeutics for spinal cord injury in mammals. Scientific Reports. 9:10475.
Abstract
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.
Errata / Notes
This article is corrected by ZDB-PUB-200116-6
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping