Abstrait

A snake toxin as a theranostic agent for type 2 vasopressin receptor-related diseases

Laura Droctovea Justyna Cioleka

 The type 2 vasopressin receptor (V2R), in normal physiological condition, is almost exclusively expressed in the kidney where it regulates water homeostasis. Its blockage is linked to several diseases, among those, the polycystic kidney disease (PKD) and the hyponatremia. Currently, only one drug succeeded to reach the market, but with many concerns (Anderegg, Kidney medicine 2020). Scorpions, spiders, snakes, conus, etc… are often seen as dangerous, frightening and ugly animals. But their venoms are extremely rich in toxins which are highly valuable in the context of human use and drug development. We optimized a process to identified GPCR active toxins linked to unmet therapeutic needs. The mambaquaretin (MQ) was discovered in the green mamba snake African venom and it is the most selective antagonist ever find for the V2R. We challenged it with successes on rodent models of PKD (pcy mice) and hyponatremia (rat model, Ciolek PNAS 2017; Droctové Theranostics 2020). MQ represents a new hope for patients affected by these diseases. In tumor conditions, V2R is also ectopically expressed in various cancers like the prostatic, the breast, the bladder ones or in the metastatic form of renal carcinoma. By grafting 89Zr on MQ, we validated this toxin, by TEP imaging, as the first ligand able to label in vivo the V2R. The couple MQ/V2R is under exploitation to develop diagnostic tools