Use zebrafish to discover and identify new drugs to treat spinal cord injuries

A research team led by Leonor Saúde, Senior Researcher at the Instituto de Medicina Molecular (iMM; Lisbon, Portugal), in partnership with the company Technophage, SA, has designed a simple and efficient platform that uses fish to discover and identify new drugs to treat. spinal cord lesions. This study, published this week in open access in Scientific reports, is the proof of concept for the use of this zebrafish platform which, combined with drug reuse, has the potential to accelerate the translation period from discovery to clinics.

Spinal cord injuries can have devastating consequences because of their importance for daily activities such as walking, but also because of their inability to regenerate, resulting in permanent disability. These lesions represent a complex clinical condition for which current treatment options have limited success in terms of neurological and functional recovery.

For a significant functional recovery, it is likely that different therapies for multiple targets will be needed, because of the complex nature of the spinal cord lesions "begins to explain Leonor Saúde", with this work we have shown that, thanks to the fish zebra, we can accelerate the discovery of new therapeutic targets for spinal cord injury ".

Leonor Saúde, Senior Researcher, Instituto de Medicina Molecular

"Here, we have designed a simple and efficient platform that allows us to test and select a large number of molecules based on their ability to accelerate the regeneration of the spinal cord in zebrafish. Spinal cord transection model in zebrafish larvae, where we test different therapeutic protocols and evaluate its effectiveness through the locomotor function of larvae over time, "says Diana Chapela, PhD student and first author of this article. The researchers validated this platform by testing molecules involved in clinical trials against spinal cord injury, namely riluzole, minocycline and D-cycloserine. The results obtained showed that these drugs can also accelerate the regeneration of the spinal cord in zebrafish.

"We then tested on our zebrafish platform more than 100 molecules already approved by the FDA (Food & Drug Administration) for other conditions and identified a molecule with motor recovery properties in zebrafish larvae. , tranexamic acid, "says Leonor Saúde. Then, the effectiveness of this drug was tested in a model of spinal cord injury in rodents. "Our results show that this molecule, which is an antifibrinolytic agent, has the ability to improve motor function in mammals with spinal cord injury," the researcher added.

These promising results show the high potential of this platform, which "combined with drug reuse, has the potential to stimulate the rapid translation of new treatments for spinal cord injury in humans," said Leonor Saúde.