Novel peptides for the treatment of pain

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Chronic pain affects 1 in 5 Australians and neuropathic pain is among the most severe forms of chronic pain. Several peptides derived from cone snail venoms have attracted recent attention as potential therapeutic agents for the treatment of neuropathic pain. One of these, conotoxin MVIIA, has recently been approved in the US and Europe and others, including CVID and ACVI, are in various stages of clinical investigation. These small disulfide rich peptides share the attractive features of peptides in general of having exquisite selectivity for particular receptors, but also share the general disadvantages of peptides of short biological half-lives and poor bioavailablility. Stabilisation of these conotoxins has the potential to substantially increase their therapeutic potential. In preliminary studies we have shown that by introducing a circular petide backbone into a conotoxin using a linker sequence we can increase its stability and resistance to enzymatic degradation. We therefore propose that it will be possible to cyclise a wide range of conotoxin molecules and thereby improve their drug like properties. In this project we will use our cyclisation approach to develop new potential treatments for pain from two classes of conotoxins. One of the lead molecules shows oral bioavailability in an animal pain model and potentially represents a major breakthrough in the field of peptide drug delivery.