Researchers have designed a simple and efficient platform that uses zebrafish to discover and identify new drugs to treat spinal cord lesions. The proof-of-concept study was published today in Scientific Reports.
Spinal cord injuries can have devastating consequences because of the importance of the spinal cord for day-to-day activities (such as walking), but they also result in a failure to regenerate, leading to permanent disabilities. These lesions are a complex clinical condition for which the current treatment options have limited success in neurological and functional recovery.
The authors believe that it’s likely that various therapies for multiple targets are needed in order for a patient to make a significant functional recovery. Combined with drug repurposing, their new zebrafish platform has the potential to accelerate the translation period from therapeutic discovery to clinics.
“Here, we have designed a simple and efficient platform that allows testing a large number of molecules and selecting them based on their ability to accelerate the regeneration of the spinal cord in zebrafish,” says first author Diana Chapela of the University of Lisbon. “Our platform consists of a model of spinal cord transection in zebrafish larvae where we test different therapeutic protocols and evaluate its efficacy through larvae locomotor function over time.”
The researchers validated this platform by testing molecules that entered clinical trials for 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 the zebrafish.
“We then tested on our zebrafish platform more than 100 molecules already approved by the Food & Drug Administration (FDA) for other conditions and identified a molecule with motor recovery properties in zebrafish larvae, the Tranexamic Acid,” says senior author Leonor Saúde, also of the University of Lisbon.
Next, the efficacy of this drug was tested in a spinal cord injury model in rodents. The drug, which is an antifibrinolytic agent, was shown to improve motor function in mammals with spinal cord injury.
Image: This is a 5-day-old zebrafish larva, in which motor neurons are marked with a green fluorescent protein. Image courtesy of Diana Chapela, iMM.