BRAIN-CHIP MODELING NEURODEGENERATION AND NEUROINFLAMMATION IN PARKINSON'S DISEASE

    公开(公告)号:US20220340849A1

    公开(公告)日:2022-10-27

    申请号:US17719627

    申请日:2022-04-13

    申请人: EMULATE, INC.

    摘要: The invention relates to modeling brain neuronal disease in a microfluidic device, comprising a co-culture of iPS-derived brain endothelial cells; iPS-derived dopaminergic neurons; primary microglia; and primary astrocytes, a Blood-Brain-Barrier (BBB)-Chip and a Brain-Chip. In particular, cross-talk between glial cells (e.g. microglia and astrocytes) with neuronal cells, in further contact with endothelial cells is contemplated for use for identifying drug targets under conditions for inducing in vivo relevant neuronal inflammation, neurodegeneration and neuronal death. Thus, in one embodiment, a microfluidic Brain-Chip comprising a co-culture of brain cells is exposed to α-synuclein preformed fibrils (PFF), a type of pathogenic form of α-synuclein. Such α-synuclein PFF exposure demonstrates an in vivo relevant disease pathogenesis on a microfluidic device as a concentration- and time-controlled manner that may be used for preclinical drug evaluation for diseases related to neuronal inflammation, e.g. Parkinson's disease (PD). In some embodiments, modulation of complement in the presence of neuronal inflammation is contemplated. In some embodiments, drug delivery to brain cells across the BBB is contemplated for preclinical testing of drug efficacy for slowing or stopping neuronal inflammation and degeneration.