Neurology; cardiovascular

Mouse studies suggest inhibiting C5 could help treat AD and atherosclerosis. In a transgenic mouse model of AD expressing mutant human amyloid precursor protein (APP) and presenilin 1 (PSEN1; PS1), an siRNA targeting liver-specific C5 decreased the number and density of β amyloid plaque-associated microglia cells in the brain parenchyma compared with a non-targeting control siRNA. In an apolipoprotein E (APOE)-deficient mouse model of atherosclerosis, the siRNA targeting liver-specific C5 decreased atherosclerotic plaque size in the aortic root and thoracic and abdominal aorta and macrophage density in plaques. Next steps by Easemedcontrol GmbH include designing and testing double-stranded RNAs targeting C5 in models of AD and atherosclerosis.

Alexion Pharmaceuticals Inc. markets Soliris eculizumab, a humanized mAb targeting C5, for hemolytic uremic syndrome, myasthenia gravis and paroxysmal nocturnal hemoglobinuria (PNH) and has the product in Phase III testing for neuromyelitis optica (NMO) and renal transplant rejection and Phase II testing for anemia and graft rejection. ...