Novel therapy for Goodpasture syndrome

Novel therapy for Goodpasture syndrome Abstract Goodpasture syndrome GS is a rare autoimmune pulmonary disorder evolving from glomerular basement membrane GBM disease GBM disease and GS are rapidly progressing leading to renal failure and death if not treated Current treatments are immunosuppressive and ineffective and carry a high risk of adverse effects Autoantibodies to the noncollagenous NC domain of the chain of type IV collagen IV NC a component of the basement membrane of glomeruli and alveoli trigger an immune response leading to antibody deposition on the basement with subsequent inflammation and necrosis Both antibody mediated cytotoxicity ADCC and complement mediated cytotoxicity CDC are involved Blocking antibodies lacking effector functions have proven effective therapies in other autoimmune disorders of similar etiology e g neuromyelitis optica During this Phase I project we will engineer a high affinity anti type IV collagen human monoclonal antibody to eliminate all residual effector functions for linkage to a robust complement inhibitor The resulting dual function fusion protein will inhibit GBM binding by pathogenic antibodies as well as locally target complement activation The outcome of this work will be a novel mechanism based therapy for Goodpasture syndrome Narrative Autoimmune glomerular basement membrane GBM disease is a severe rapidly progressing kidney disease Without treatment it is often fatal None of the available treatments is effective We have identified a monoclonal antibody that will be the first disease modifying therapy for GBM disease