Porosome reconstitution reverses Alzheimers in human brain organoids

ABSTRACT A central challenge in overcoming diseases resulting from defects in the cellular nanoscale multiprotein porosome complexes, is the consequent alteration of other proteins within the complex. By exploiting the distinct porosomes present in different tissues, Porosome Therapeutics, Inc., has developed a clinically relevant approach to incorporate (reconstitute) functional wild type porosomes into the plasma membrane of diseased cells to overcome secretory defects. In a combinatorial strategy of reprogramming the neuronal secretory and metabolic components, we established a dual-target therapeutic framework that repairs synaptic and metabolic defects to counteract neurodegeneration in Alzheimer’s. Utilizing iPSC derived human brain organoids, as recommended by the NIH and FDA, we demonstrate both the morphological and functional reversal of Alzheimer’s following porosome-apigenin treatment. Using the UHD-CMOS-MEA System developed jointly by Sony Semiconductor Solutions (Sony), SCREEN Holdings (SCREEN) and VitroVo, we were able to monitor thousands of neuronal firing in the brain organoids, helping in assessing the restoration of neuronal function in Alzheimer’s following porosome-apigenin therapy.