Anti Inflammatory TnP drug poses no threats to Danio Rerio brain

Early preclinical screening using zebrafish (Danio rerio) reveals the safety of the candidate anti-inflammatory therapeutic agent TnP

 

EMAnalysis A rapid zebrafish profilling assay for neurodevelopmental toxicant identification

Zebrafish as a model organism to study inflammatory diseases

 

Highlights

TnP has been indicated for chronic inflammatory diseases, multiple sclerosis
• Zebrafish is an alternative animal model for preclinical drug development
• Preclinical toxicology studies have shown that TnP has a wide therapeutic index range from 1 nM to 10 μM
TnP did not induce cardiotoxic effect or cardiac dysfunction
TnP crossed the blood-brain barrier without causing neurotoxicity

Abstract

The patented anti-inflammatory peptide TnP had its effectiveness recently confirmed in vivo in a murine model of multiple sclerosis and asthma. In this work, the safety of the TnP was evaluated in investigative toxicology tests using zebrafish (Danio rerio) as a model. We conducted the OECD #236 test to investigate effects of the TnP on the survival, hatching performance, and morphological formation of zebrafish embryos. After determining these endpoints, morphometric analysis termination of locomotion eartbeat rate in zebrafish larvae were evaluated to identify adverse effects such as neurotoxicity and cardiotoxicity. The results highlight a wide therapeutic index for TnP with non-lethal and safe doses rom 1 nM to 10 μM, without causing neurotoxicity or cardiotoxic effect. The low frequencyf abnormalities by TnP was associated with high safety of the molecule and the developing embryo's ability to process and eliminate it. TnP crossed the blood-brain barrier without disturbing the normal architecture of forebrain, midbrain and hindbrain. Our data reinforce the importance of zebrafish as an accurate investigative toxicology model to assess acute toxicity as well as cardiotoxicity and neurotoxicity of molecules in the preclinical phase of development.

 

Link to the publication :

https://www.sciencedirect.com/science/article/pii/S2214750020304467