Developing a natural peptide as a novel potent non-opioid analgesic – PeptOPain

There is crucial and unmet need for efficient therapies against chronic pain. Mambalgins represent a real opportunity to develop novel analgesics. These natural peptides specifically block Acid-Sensing Ion Channels, a set of ion channels emerging as important targets in pain. The three isopeptides produce the same potent opioid-independent analgesic effects in rodents that can be as strong as morphine but with a different mechanism of action, fewer unwanted side effects and without apparent toxicity. Mambalgins have been shown to be effective in models of inflammatory and neuropathic pain after local, intravenous or central administration. In addition, in a mouse model of inflammatory pain, a comparative study has recently shown that mambalgin-1 induces faster and stronger analgesia compared to ziconotide / Prialt (a peptide derived from marine cone snail venom with an AMM since 2005).

In this project, we propose (i) to evaluate the stability of mambalgin-1 in biological fluids, (ii) to characterize its biodistribution and pharmacodynamic properties using PET imaging (after 18F labelling) and (iii) to determine its immunogenicity and propose a de-immunization strategy. In addition and in parallel with these studies, engineering approaches to mambalgin-1 will be carried out in order to obtain one or two miniaturized, more stable and de-immunized variants.

This project is dedicated to the maturation of a promising innovative therapy against pain with the objective of further industrial transfer. It will provide valuable preclinical data on mambalgin-1 (or one optimized analog) that are mandatory for the development towards the clinic.