Novel Drug Candidates Improve Ganglioside Accumulation and Neural Dysfunction in GM1 Gangliosidosis Models with Autophagy Activation

• DOI: 10.1016/j.stemcr.2020.03.012
• Publication Date: 2020-04-16T14:29:55Z
• Authors: Ryutaro Kajihara; Tadahiro Numakawa; Haruki Odaka; Yuji Yaginuma; Noemi Fusaki; Toshika Okumiya; Hirokazu Furuya; Seiji Inui; Takumi Era
• Keywords: Gangliosidosis; Ganglioside; Sandhoff disease; Lysosomal storage disease

GM1 gangliosidosis is a lysosomal storage disease caused by loss of β-galactosidase activity and characterized progressive neurodegeneration due to massive accumulation ganglioside in the brain. Here, we generated induced pluripotent stem cells (iPSCs) derived from patients with gangliosidosis, resultant neurons showed impaired neurotransmitter release as presynaptic function ganglioside. Treatment normal also disturbed function. A high-content drug-screening system was then established identified two compounds drug candidates for gangliosidosis. patient-derived candidate agents activated autophagy pathways, reducing vitro vivo, restoring dysfunction. Our findings thus demonstrated potential value iPSC lines cellular models revealed therapeutic future clinical application.