Investigating the antifibrotic effect of the antiparasitic drug Praziquantel in preclinical models

23 Sep 2020
23 Sep 2020

Dr Justin Nono Komguep authored a paper with Professor Frank Brombacher and support from ICGEB students and fellows Thabo Mpotje, Dr Nada Abdel Aziz, Dr Lerato Hlaka, Paballo Mosala and Dr Severin Donald Kamdem in Scientific Reports in June 2020. The paper is entitled “Investigating the antifibrotic effect of the antiparasitic drug Praziquantel in in vitro and in vivo preclinical models”.

The International Centre for Genetic Engineering and Biotechnology (ICGEB) group produced the paper that was published in collaboration with Merck Global Health Institute. This was an all-round team effort led by Dr Nono under the supervision of Professor Frank Brombacher and Dr Thomas Spangenberg (Head of Global Health Drug Discovery at Merck Group) and the support from DOI students and fellows and scientists from EMD Serono Research and Development Institute in the United States.

Tissue fibrosis underlies most human deaths with almost 50% of all reported deaths having a fibrotic origin. The progression of fibrosis is very complex and seems to be irreversible once it has begun. There are some reported preventive options however “therapeutic options are still scarce and in very high demand, given the rise of diseases linked to fibroproliferative disorders”.

The researchers explored four platforms in correlation to screen preventive and therapeutic potentials of the antiparasitic drug Praziquantel as a possible antifibrotic.

The team from the DOI and collaborators from the US complementarily “applied the mouse CCl4-driven liver fibrosis model, the mouse chronic schistosomiasis liver fibrosis model, as well as novel 2D and 3D human cell-based co-culture of human hepatocytes, KCs (Kupffer cells), LECs (Liver Endothelial Cells), HSCs (Hepatic Stellate Cells) and/or myofibroblasts to mimic in vivo fibrotic responses and dynamics”. This provided “a novel sophisticated multi-assay screening platform to test preventive and therapeutic antifibrotic candidates”.

On this multi-assay platform, the team demonstrated that Praziquantel has “some effect on fibrosis marker when preventively administered before severe establishment of fibrosis. However, the drug failed to potently reverse already established fibrosis”.

Read the paper - Investigating the antifibrotic effect of the antiparasitic drug Praziquantel in in vitro and in vivo preclinical models

Article by Bonamy Holtak