Cascade Biotechnology INC | Complement Therapeutics; novel approach to CNS/PNS disease management using the innate complement system.

Neurological Diseases

Neuromyelitis Optica-Autoimmune

  • Neuromyelitis optica (NMO) is an autoimmune inflammatory disease that selectively targets the optic nerves and spinal cord, leading to blindness and paralysis (J. Ratelade, et al. (2013) Involvement of antibody- dependent cell-mediated cytotoxicity in inflammatory demy- elination in a mouse model of neuromyelitis optica. Acta Neuropathologica, vol. 126, no. 5, pp. 699–709). 

  • Since NMO patients often present demyelinating lesions in the central nervous system (CNS), it has long been considered a variant of multiple sclerosis (MS); however, recent data suggest that its pathogenesis may be different (M. Jurynczyk et al. (2015) Overlapping CNS inflammatory diseases: differentiating features of NMO and MS,.Journal of Neurology, Neurosurgery, and Psychiatry, vol. 86, no. 1, pp. 20–25). 

  • The immunopathology of NMO includes restricted demyelination and inflammation of the optic nerves and several spinal segments (Li and Y. Yan. Experimental models of neuromyelitis optica: current status, challenges and future directions. Neuroscience Bulletin, vol. 31, no. 6, pp. 735–744, 2015). 

  • Combination Treatment of C16 Peptide and Angiopoietin-1 Alleviates Neuromyelitis Optica in an Experimental Model (Mediators of Inflammation Volume 2018, Article ID 4187347).

  • In contrast to multiple sclerosis, autoantibodies against aquaporin-4 (AQP4) expressed on astrocytic end-feet have been exclusively detected in sera of NMOSD patients. 

  • Several lines of evidence suggested that anti-AQP4 autoantibodies are pathogenic, but the mechanism triggering inflammation, impairment of astrocyte function, and the role of neutrophils presented in NMOSD cerebrospinal fluid remains unknown. pathogenicity of NMOSD serum, which by consecutive action of anti-AQP4 Abs, complement system, and neutrophils affected astrocyte function. Anti-AQP4 Ab binding astrocytes initiated two parallel complementary reactions. 

  • The first one was dependent on the complement cytotoxicity via C5b-9 complex formation, and the second one on the reverse of complex formation, and the second one on the reverse of astrocyte glutamate pump into extracellular space by C5a pre-activated neutrophils. Piatek P, et al. (2018) C5a Pre-activated Neutrophils Are Critical for Autoimmune-Induced Astrocyte Dysregulation In  Neuromyelitis Optica Spectrum Disorder .Front Immunol.  23 July 2018 doi: 10.3389/fimmu.2018.01694).