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Bilateral Austria-Flemish Joint Research Project

“Neuropeptide Engineering for Improved Chronic Pain Treatment”

Chronic pain remains one of the main challenges in human medicine at the beginning of the third millennium. Incapacitating pain is a constant backdrop in daily life, resulting in personal suffering, high health costs and economic burden for the society. Around 20-30% of all people worldwide suffer from chronic pain, and will certainly continue to grow as population ages. Central goals in chronic pain control aim to provide pain relief of adequate efficacy and duration.

The current pharmacotherapy of chronic pain has proven to offer unsatisfactory solutions and stresses the need for alternative mechanism-based treatment strategies. This project comprises theoretical and experimental work undertaken in the fields of pain research, analgesic drug discovery and opioid pharmacology, aiming to identify newly designed opioid drugs with reliable target-oriented pharmacology, efficacy, and safer use for the management of chronic pain conditions. The project is based on the knowledge that natural ligands which modulate pain in humans are neuropeptides (endorphins, enkephalins, etc.). Without chemical modifications to provide enhanced stability and selectivity, neuropeptides are poorly suited for clinical applications. The innovative research avenue consists of the judicious engineering of neuropeptides to generate stable and selective “peptidemimetics” as novel analgesics with improved pharmacology and safety profiles. The strategy is based on the concept of multitarget ligands with a well-chosen activity and in which two active peptide pharmacophores are combined into one molecule. They can interact with multiple biological targets to induce a desired activity at each individual target, to prolong the analgesic activity and to provide more general painkillers active in acute and chronic pain. Drugs with such novel biological profiles are expected to have medical benefits for the treatment of pain.

Multidisciplinary, synergistic strategies are applied to achieve the goals of the planned research, where state-of the-art methodologies are used ranging from computational modeling to medicinal chemistry to pharmacology and disease animal models, suitable to endow the proposed research with high translational potential.

Scientific teams led by Mariana Spetea (Opioid Research Group, University of Innsbruck http://www.uibk.ac.at/pharmazie/phchem/opioid.html) and Steven Ballet (Research Group of Organic Chemistry, Vrije Universiteit Brussel https://orgc.research.vub.be/) are combining their know-how and long-standing expertise in achieving the goals of the research program.

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