Induced pluripotent stem cells (iPSCs) and iPSC-derived cerebral organoids as a model of Succinic Semialdehyde Dehydrogenase Deficiency

Abstract

Succinic semialdehyde dehydrogenase defi-ciency (SSADHD) represents a rare monogenetic diseasecausing disturbed degradation of γ-aminobutyric acid (GABA) due to variants in ALDH5A1. Succinic-semialdehyde cannot be oxidized to succinate and is consecutively reduced to γ-hydroxybutyrate (GHB). The phenotype is comprised of developmental delay, motor difficulties, behavioral problems, and epilepsy. It is unclear how altered concentrations of GABA and GHB contribute to the pathophysiology of SSADHD. We used patient-derived inducedpluripotent stem cells (iPSCs) to generate a three-dimensional cell culture model to study early neuronaldevelopment in SSADHD. Immunohistochemistry and whole-cell patch clamp were used to determine morphological and electrophysiological properties.

Date
Sep 4, 2019 10:00 AM — 10:15 AM
Location
De Doelen ICC Rotterdam, The Netherlands
Schouwburgplein 50, Rotterdam, 3012 CL
Avatar
Heiko Brennenstuhl, MD, MBA
Medical Professional & Postdoctoral Research Fellow

I am interested in inherited metabolic disorders and neurosmuscular diseases with a movement pehnotype. I specialize in stem cell research and challenges and opportunities of high-throughput data analysis.