Guthy-Jackson Foundation and UCLA Accelerate Neuromyelitis Optica Therapeutic Discovery Using CytoSolve® In Silico Systems Architecture for Immune Pathway Integration

Partner Description

Guthy-Jackson Charitable Foundation & University of California, Los Angeles
The Guthy-Jackson Charitable Foundation (GJCF) supports foundational research to understand the pathogenesis of neuromyelitis optica (NMO), a rare autoimmune disorder affecting the optic nerves and spinal cord. Working with investigators at UCLA, the collaboration focuses on mechanistic, pathway-level understanding of NMO, particularly the role of anti–aquaporin-4 (AQP4) IgG antibodies in driving central nervous system inflammation, with the goal of enabling more effective therapeutic strategies.

Challenge

Neuromyelitis optica arises from complex, multi-cell immune signaling within the central nervous system, involving astrocytes and multiple immune cell populations. These interactions generate emergent inflammatory behaviors that are difficult to capture using isolated pathway analyses or animal models alone. Differences between human and mammalian immune signaling complicate translational inference, while the absence of a unified computational framework limited the ability to test, extend, and integrate GJCF’s proposed signaling-pathway blueprint for NMO pathogenesis.

How CytoSolve® Helped

CytoSolve® converted the GJCF-proposed NMO pathway blueprint into a modular, integrative in silico systems architecture. Molecular pathways implicated in NMO were encoded as mechanistic computational models with explicit signaling logic and regulatory structure. These models were assembled into a multi-compartment, multi-cell framework capturing signal transduction and cross-talk among astrocytes, dendritic cells, T cells, and B cells.

Rather than analyzing pathways in isolation, CytoSolve® integrated them into a unified computational context to explore system-level immune behavior. The architecture explicitly modeled anti-AQP4 IgG as a mechanistic perturbation, enabling simulation of antibody-driven immune activation and downstream inflammatory cascades. Cytokine-level readouts linked IgG–AQP4 signaling to activation patterns in interleukins 2, 4, 8, 10, and 13, supporting hypothesis generation around inflammatory signatures and immune amplification loops relevant to NMO.

Key Benefits Realized

  • System-level interpretability through integration of CNS-relevant cell types and immune pathways into a single mechanistic framework.
  • Insight into cross-cell signaling dynamics driving astrocyte–immune cell–mediated inflammation.
  • Support for in silico experimentation to evaluate antibody-driven perturbations and downstream signaling consequences.
  • Mechanistic linkage between anti-AQP4 IgG activity and cytokine activation patterns including IL-2, IL-4, IL-8, IL-10, and IL-13.
  • Improved translational strategy by reducing reliance on animal-only inference and emphasizing human immune-pathway modeling.

Outcome

By converting the GJCF pathway blueprint into an integrated CytoSolve® in silico systems architecture, the GJCF–UCLA collaboration gained a mechanistic platform for examining neuromyelitis optica as a coordinated, multi-cell immune signaling disease. The resulting models enabled a unified view of how anti-AQP4 IgG drives cytokine activation and immune amplification across astrocytes and key immune populations, strengthening hypothesis generation, informing experimental design, and supporting more effective prioritization of therapeutic intervention strategies grounded in integrated pathway behavior