Testing a novel viral approach to targeting macrophages

Research project carried out in fulfilment of the Brain Sciences MSc at the University of Glasgow Neuropathic pain is a widespread disease that is often resistant to current analgesic treatments. It is commonly triggered by injury, after which disruptions of normal pain signalling pathways continue to cause spontaneous pain sensations and increased pain sensitivity. Macrophages, resident immune cells, have been implicated in the initiation and maintenance neuropathic pain by increasing proliferation, infiltration, and moving to a pro-inflammatory state, not only at the site of injury, but also in the dorsal root ganglia (DRG) of the spinal cord. Macrophages have therefore become a potential target for novel therapeutics. A possible targeting method is adeno-associated viruses (AAV), which can be modified with specific proteins to enable them to target specific cell types. In the present study, the ability of a novel virus to selectively transduce macrophages in the DRG was investigated. The novel virus featured a macrophage-specific promoter, and was added to various cell cultures, including an immortalised murine microglia cell line, and ex vivo cultures of murine and canine DRG cells. It was found that the AAV showed limited transduction efficacy in the various cultures. In addition, species differences were noted in the number and morphology of macrophages between the murine and canine DRG cultures. Further, iPSC-derived macrophages (iMacs) were generated successfully, and proposed as a more relevant model of macrophages in human neuropathic pain. Overall, this study presents a novel approach for therapeutic development in neuropathic pain by targeting DRG macrophages, and a potential model of human macrophages in iMac co-cultures.