Translational research on prolyl oligopeptidase inhibitors: the long road ahead

Despite the fact that some have passed early phases of clinical trials, no prolyl oligopeptidase inhibitors are currently on the market. Yet, since 2003, there has been a boost in patent applications claiming prolyl oligopeptidase inhibitors for the treatment of Alzheimer's and Parkinson's diseases, and other neurodegenerative and psychiatric disorders. While experts in the field call for innovative scaffolds to develop more potent inhibitors with more favorable properties, they also relate a lack of knowledge of the toxicology, bioavailability, pharmacokinetics and pharmacodynamics of existing compounds that hinders their assessment. Yet, with the current insights, it is difficult to correlate specific inhibitor effects with the postulated functions of prolyl oligopeptidase in the brain.