Neuromyelitis Optica Spectrum Disorder (NMOSD) in a Patient with Noonan Syndrome and Prior Juvenile Myelomonocytic Leukemia

neuroprotective strategies for progressive MS.NLRX1 is an innate immune sensor that negatively regulates several inflammatory pathways, including NF-B. Design/MethodsActive, spontaneous, and adoptive transfer EAE models were used to evaluate the impact of NLRX1.Retinal ganglion cell (RGC) count, optic nerve axonal degeneration, gliosis, and T-cell infiltration were assessed by immunohistochemistry (IHC).Adoptive transfer experiments transferred MOG-specific T-cells into Rag -/-and Nlrx1 -/-Rag -/-mice.Lastly, LPS-stimulated mixed-glial cultures and EAE mice were treated with novel NLRX1 agonists. ResultsThis study revealed significantly worse RGC loss and decreased optic nerve neurofilament light chain expression in Nlrx1 -/-mice compared to WT mice in both active and spontaneous EAE, despite no change in the infiltration of peripheral T-cells.Adoptive transfer EAE experiments showed that Nlrx1 -/-Rag -/-mice had increased Iba1 and GFAP expression in their optic nerves compared to compared to Rag -/-mice.Two novel NLRX1 agonists, NX-13 and LABP-66, were able to decrease NF-B inflammatory gene expression in LPS-simulated mixed glia in an NLRX1-dependent manner.Oral treatment with LABP-66 in active EAE mice after disease onset resulted in significantly higher RGC density (less RGC loss) compared to vehicle-treated mice. Conclusions