A novel long-acting therapeutic displays potential for treating chronic pain

The numerous forms of chronic pain cause severe, persistent suffering, debilitation/inability to work and poor quality of life.  These pose major healthcare challenges/costs >€200 billion each year in Europe, with expenditure on patients having inflammatory conditions such as arthritis exceeding €25 billion/year.  Unfortunately, conventional pain killers and anti-inflammatory medicines (to a lesser extent) are mainly palliative, relatively short-acting and often exert side effects.  Thus, there is a pressing unmet need for effective analgesics which are both long-acting and non-addictive (unlike morphine, in current use).

Researchers in the International Centre for Neurotherapeutics at DCU have employed a novel strategy for designing biotherapeutics that potently block the release of pain signalling- and inflammatory-messengers from sensory neurons and immune cells.  One component is a very specific enzyme that truncates and inactivates a SNARE protein that is essential for their regulated secretion.  The other constituent contributes by targeting the protease to just the two cell types involved in these abnormalities, and delivers the active moiety intra-cellularly.  There it can act over an extended period to normalise release of the above-noted mediators that initiate chronic pain.

The selectively-targeted compound, prepared by protein engineering using harmless bacteria, has been evaluated to-date using various cell types that release pro-inflammatory agents (e.g. cytokines), in parallel with sensory and other neurons.  Although this new generation of exocytosis inhibitors exhibit promising potential in vitro, planned experiments in animal models of these disease conditions, presently supported by a Commercialisation Fund grant from Enterprise Ireland, will establish its efficacy in vivo and suitability for clinical assessment.  If warranted, a trial ‘first-in-humans’ will be facilitated by generating the compound under Good Manufacturing Practice (GMP) in a newly-constructed, state-of-the-art GMP suite funded by the Higher Education Authority under the PRTLI 4 for ‘Target-driven Therapeutics and Theranostics’.