UCLA accelerate neuromyelitis optica therapeutic discovery using CytoSolve®’s integrative systems architecture for immune-pathway modeling across cellular interactions

UCLA supports foundational research to understand the pathogenesis of neuromyelitis optica (NMO), a rare autoimmune disorder affecting the spinal cord and optic nerves. Working with UCLA investigators, the partnership focuses on mechanistic, pathway-level understanding of NMO—particularly the role of anti–aquaporin-4 (AQP4) IgG antibodies in central nervous system (CNS) inflammation—to enable more effective prevention strategies and therapies.

Challenge

NMO pathogenesis emerges from complex, multi-cell immune signaling within the CNS—an interplay that is difficult to reproduce and interpret using single-pathway views or animal models alone. Key obstacles included:

Human immune-system complexity: Multiple immune cell types interact dynamically, producing emergent behaviors not captured by isolated experiments.

Translational gaps from mammalian models: Immune signaling in common research animals can differ materially from humans, complicating therapeutic inference.

Need for a unifying mechanistic framework: GJCF proposed a signaling-pathway “blueprint” for NMO pathogenesis, but it required computational formalization to be testable, extensible, and integratable.

How CytoSolve Helped

CytoSolve® transformed the proposed pathway blueprint into a systems architecture of interoperable in silico models, enabling a continuum-style integrative view of NMO immune signaling. The approach emphasized modularity and integration:

Blueprint-to-model translation: Molecular pathways implicated in NMO were encoded into computational models with explicit mechanistic relationships and signaling logic.

Multi-compartment, multi-cell architecture: CytoSolve® modeled signal transduction and cross-talk among astrocytes, dendritic cells, T cells, and B cells, reflecting the biological diversity driving NMO pathology.

Integration of multi-signaling pathways: Rather than analyzing pathways in isolation, CytoSolve® integrated them into a unified computational context to study system-level behavior.

Antibody-driven perturbation modeling: The architecture explicitly incorporated the role of anti-AQP4 IgG as a mechanistic trigger influencing downstream immune activation and inflammatory cascades.

Cytokine-level readouts for mechanistic interpretation: The integrated model connected IgG/AQP4-driven signaling to cytokine activation patterns, including interleukins 2, 4, 8, 10, and 13, enabling hypothesis generation around inflammatory signatures and immune amplification loops.

Key Benefits Realized

  • System-level interpretability: Connected CNS-relevant cell types and pathways into a single, coherent mechanistic framework rather than disconnected pathway diagrams.
  • Cross-cell signaling insight: Enabled exploration of how astrocyte–immune cell interactions propagate inflammation in NMO-relevant contexts.
  • In silico experimentation: Supported virtual perturbation analysis (e.g., antibody-driven triggers and downstream signaling consequences) to guide experimental focus.
  • Cytokine signature linkage: Mechanistically related anti-AQP4 IgG activity to activation patterns in IL-2, IL-4, IL-8, IL-10, and IL-13.</li

Outcome

By converting UCLA ’s pathway blueprint into an integrated CytoSolve® in silico systems architecture, the UCLA collaboration gained a mechanistic platform to examine NMO as a coordinated, multi-cell signaling disease. The resulting models supported a more unified view of how anti-AQP4 IgG can drive cytokine activation and immune amplification across astrocytes and key immune populations—strengthening hypothesis generation, informing experimental design, and helping prioritize intervention concepts grounded in integrated pathway behavior.