Complement C1q

Class

Fab fragment binding C1q, selectively blocking classical complement pathway activation

Complement C1q is the initiating recognition molecule of the classical complement pathway, a branch of the innate immune system that helps identify and clear pathogens, immune complexes, and unwanted cellular material such as apoptotic cells or, notably, synapses. C1q assembles with two associated proteases (C1r and C1s) to form the C1 complex; when C1q binds its targets, it activates this complex, setting off a proteolytic cascade that generates inflammatory mediators and tags structures for removal by phagocytic cells. In the nervous system, this same tagging mechanism can mark synapses for elimination by microglia, a process implicated in synapse loss seen in several neurodegenerative and neuro-ophthalmic conditions. Selectively blocking C1q, rather than complement broadly, aims to interrupt this classical-pathway-driven tagging while leaving the alternative and lectin complement pathways intact, preserving other innate immune functions such as pathogen opsonization through those alternate routes. Using an antibody fragment (Fab) rather than a full antibody removes the Fc region responsible for engaging immune effector receptors, which can aid tissue penetration and limit unwanted immune activation. This mechanism is being explored across neurodegenerative and retinal diseases where synapse or neuron loss driven by classical complement activation is thought to contribute to disease progression.