PharmAust Limited (ASX:PAA) has agreed to an extension of work being conducted at the Olivia Newton-John Cancer Research Institute’s (ONJCRI) investigating the mechanism of action of monepantel (MPL) upon cancer cells.
The extension allows for the partners to continue preclinical work focusing on anti-cancer activity and MPL target protein signalling pathways.
This work, which will be conducted by the ONJCRI and funded by PharmAust, is also anticipated to provide clues to mechanisms of action against COVID-19 and motor neurone disease.
“Pleased to continue relationship”
PharmAust’s chief scientific officer Richard Mollard said: “PharmAust is pleased to continue this productive relationship with the ONJCRI.
“PharmAust is looking forward to seeing at the molecular level how MPL works in cells to combat disease, especially in terms of how MPL’s mechanism of action differs to other mTOR inhibitors presently in the clinic.”
RNA sequencing
Researchers in the Cell Death and Survival Laboratory at the ONJCRI have conducted a comprehensive RNA-Seq (RNA sequencing) screen investigating how the entire genome of cancer cells responds when treated with MPL.
A select subset of genes was found to be either switched on or off by MPL in cancer cells, but not in non-cancer cells.
The mRNA profiles of non-cancer cells were relatively unaffected by MPL treatment, consistent with the possible low level of toxicology observed for MPL.
Program of work
Using state-of-the-art techniques, ONJCRI researchers will now examine these genes in greater detail and match changes in their activity with changes in associated protein signalling pathways.
These experiments are aimed at determining what happens within the cancer cell once MPL interacts with its primary molecular targets and then exerts its downstream and definitive anti-cancer activity.
Establishing MPL’s mechanism of action in this detail will enable differentiation of MPL’s effects on cancer cells as compared to other anti-cancer drugs.
This will assist with regulatory submissions and facilitating licensing and marketing as PharmAust moves towards Phase III and IV trials.