A research team led by Leonor Saúde, lead researcher at iMM and Invited Associate Professor at the Faculty of Medicine of the University of Lisbon, in partnership with the iMM-based company Technophage, SA, have devised a simple and effective platform that uses zebrafish to discover and identify new drugs to treat spinal cord injuries. This open-access report published this week on the scientific journal Scientific Reports*, is the proof-of-concept that, combined with drug repositioning strategies, it has the potential to accelerate the period from the discovery of new therapeutic targets to their clinical use.
Spinal cord injuries can have devastating consequences because of their importance in everyday activities such as walking, but also because of their inability to regenerate, leading to permanent disabilities. These injuries are a complex clinical condition for which current treatment options have limited success in neurological and/or functional recovery. “Due to the complex nature of spinal cord injuries, it is likely that for significant functional recovery different targeting therapies are needed,” says Leonor Saúde, adding, “with this work we have shown that by using zebrafish we can accelerate the discovery of new therapeutic targets for spinal cord injuries.”
“With this project we designed a simple and effective platform that allows to test a large number of molecules and select them based on their ability to accelerate zebrafish spinal cord regeneration. Our platform is a model of spinal cord transection in zebrafish larvae where we have tested different therapeutic protocols and evaluated their effectiveness through larval behaviour and its locomotor function over time", explains Diana Chapela, PhD student and leading author of this project. The researchers first validated this platform by testing human spinal cord injury molecules that underwent clinical trials, such as Riluzole, Minocycline and D-Cycloserine. The results showed that these drugs can also accelerate spinal cord regeneration in zebrafish.
“We then tested on our zebrafish platform more than 100 FDA-approved molecules for other conditions and identified a molecule with motor recovery properties in zebrafish larvae, Tranexamic Acid,” says Leonor Saúde. The efficiency of this drug was then tested in the spinal cord injury model of a rodent. "Our results show that this molecule, which is a procoagulant agent, has the ability to improve motor function in spinal cord injured mammals," the researcher adds.
These promising results show the significant potential of this platform, which “combined with drug repositioning strategies, has the ability to accelerate the rapid adaptation of new treatments for spinal cord injuries in humans.”
This project was developed in a partnership between Leonor Saúde's laboratory and Technophage, SA, and was funded by Technophage, SA and the Foundation for Science and Technology.
* Diana Chapela, Sara Sousa, Isaura Martins, Ana Margarida Cristóvão, Patrícia Pinto, Sofia Corte-Real & Leonor Saúde (2019) A zebrafish drug screening platform boosts the discovery of novel therapeutics for spinal cord injury in mammals. Scientific Reports.