June 14-17, 2023
Meet us at ISSCR 2023 and see how NeuCyte is enabling CNS drug discovery with our advanced iPSC-derived platforms
Visit us at booth 932, chat with our scientists and find out how NeuCyte can support your CNS drug discovery needs with our hiPSC-based disease modeling and compound screening capabilities
Check out our posters
Poster #487: Miniaturized Isogenic iPSC-Derived 3D NeuroImmune Assembloids for High-Throughput Drug Screening
Date and time: Wednesday, June 14, 6:00 PM
Track: Modeling Development and Disease (MDD)
Abstract: Microphysiological systems (MPS) with defined cellular compositions provide scalable and reproducible brain models that better recapitulate the in vivo environment, in which pre-clinical drug discovery efforts can translate to a higher success rate for identified targets and compounds. Robust differentiation methods to generate neurons, astrocytes, and microglia from any genetic background enables generation of SynFire® isogenic Neurolmmune Assembloids (NIA) in which the 3D microenvironment recapitulates salient ex vivo brain phenotypes enabling improved translatable high-throughput pre-clinical drug discovery. NIAs use very few cells and yield a defined reproducible ratio of mature cells making them scalable and assay-ready. Here, we describe our isogenic platform for high-throughput drug screening. Because the platform is also modular, the impact of a mutation can be studied in a cell-type specific manner to model non-cell autonomous phenotypes mimicking the cellular complexity of the human brain. Our platform can be adapted for high-throughput drug screening yielding a cost-effective CNS-relevant drug discovery platform.
Lead Author: Martin Nicholson, PhD, Lead Scientist,
NeuCyte
Poster #707: Development of iPSC-Derived Pre-Clinical Drug Screening Assays for KIF1A Associated Neurological Disorder (KAND)
Date and time: Thursday, June 15, 1:30 PM
Track: Modeling Development and Disease (MDD)
Abstract: KIF1A Associated Neurological Disorder (KAND) is a rare and progressive neurodegenerative disorder caused by mutations in the KIF1A gene. Affecting over 500 diagnosed individuals, this disorder has a broad phenotypic presentation, including spastic paraplegia, seizures, hypotonia, optic nerve atrophy, cerebral and cerebellar atrophy, and intellectual disability. Despite the overwhelming need for therapeutics, there are no clinical trials, let alone approved therapies for KAND in which the lack of established and reproducible assays for therapeutic discovery and development is a major barrier. Therefore, we generated iPSC-derived glutamatergic and GABAergic neurons from E253K and P305L KIF1A mutation patients in order to develop pre-clinical assays for KAND drug discovery. Here, we describe phenotypic assays that represent the clinical manifestations of KAND, i.e., developmental delay and seizures, that can be used to screen for therapeutics. KIF1A mutations lead to impairments in neurotrophic support of axonal outgrowth, cargo trafficking deficits, as well as altered neuronal electrophysiology in iPSC-derived neurons. These KIF1A mutant phenotypes further our understanding of KAND biology and represent translatable biomarkers that can be readily adapted to high-throughput screening platforms to identify KAND therapeutics.
