These diseases are characterized by an abnormal autoreactive immune response to otherwise healthy tissue in the body. This erroneous immune response leads to activation of C1q, the initiating molecule of the classical complement cascade, which then drives tissue damage. By targeting C1q in preclinical studies, Annexon has shown the ability to block activation of the classical complement pathway and protect against tissue damage in multiple models, including Neuromyelitis Optica, Guillain Barre Syndrome and Cold Agglutinin Disease.
Microglial cells (immune cells that reside in the brain) are erroneously called to action by C1q and the classical complement cascade in neurodegenerative disease. They recognize and engulf complement-coated synapses, secrete inflammatory cytokines and ultimately contribute to neuron loss. Inhibition of C1q is protective in several animal models of disease, including Alzheimer’s Disease, Huntington’s Disease, Frontal Temporal Dementia and Spinal Muscular Atrophy.