Neurologist Peter Calabresi recaps his presentation, “Oligodendrocyte Precursor Cell Present Antigen and Are Cytotoxic Targets in Inflammatory Demyelination,” from the American Neurological Association 2020 Virtual Meeting. His lab is developing a new model to understand why oligodendrocyte precursor cells (OPCs) might fail to make myelin in the context of multiple sclerosis plaque and the value of identifying transcriptomic profiles of OPCs that are amenable to therapeutic intervention.
Hello. Thank you for listening to this summary of the Raymond Adams lecture presented at the A 2020 virtual meeting. My name is Peter Calabrese. You know, my professor of neurology at Johns Hopkins University. This research talk was about Allah go dangerous site precursor cells or oh, PCs and their potential to help repair myelin in multiple sclerosis in M s. We've had enormous success in developing treatments for elapsing remitting disease, and these therapies mostly target peripheral immune cells. But we've been unable to cracked the problem of my own repair, probably because our therapies don't get into the central nervous system and impact on the glial cells we've been studying, oh, PCs and their potential to turn into my living cells for a number of years. As of other people around the world, several clinical trials of my own repair drugs have been completed using drugs that show promise in the lab to promote oh, PCs. But they have not achieved the success that we were hoping for in early clinical trials. Oh, PCs are abundant proliferate of cells in the adult brain that had the capacity to turn into my lovemaking cells, cutting edge basic Neuroscience research has identified several promising targets on these cells, which may allow enhancement of their differentiation into milon making cells. But as I said, the clinical trials to date either been completely negative for primary outcome measures or their capacity to improve function has been modest. The explanation for this discordance between pre clinical success and disappointing trial outcomes has remained an enigma. My laboratory has developed a new model to better understand why OPC is might fail to make myelin in the context of an M s plaque. In this model, we cause de Molen ation with a toxin called Cooper Zone. And we also transfer my own reactive T cells that traffic to the brain sites of de Molen ation and suppress free myelin ation either directly or through the production of reactive glial cells. We found that not only did the T cells inhibit my own repair, but interestingly, the inflammation transformed the OPC es into inflammatory cells that we call immuno PCs or I o P C s the I o P. C. S have the capacity to process and present manage into CD eight T cells, which in turn, to kill the OPC es So in this novel paradigm, the Iot PCs may propagate further inflammation, and there's a depletion of the OPC pool. We think this is very relevant, clinically and for the purposes of clinical trials, because not only does it explain why remind the nation might fail in the context of ongoing inflammation, but it suggests the possibility that the OPC is that we're trying to coax into Milon, making cells actually become bad actors, if you will, and further propagate the inflammation. This research also explains why there's so many CD eights in the brain, which we've never been able to explain before on the basis of any kind of viral infection. The relevance of this therapeutically is that we now have identified transcript Tomic profiles of these oh PCs that are amenable to therapeutic intervention. I eat if we can turn off the inflammatory pathways in these oh, PCs. We hope that we can not only stop the glial inflammation, but that we could actually promote myelin repair by allowing these cells or perhaps new oh PCs to take over the plaque milieu and turn into milon making cells. Thanks very much for your attention. Mhm