ALS Disease Modeling with iPSC-Derived Neurons and HD-MEA Phenotyping
January 22, 2025 | 17:00 CET
08:00 PST | 11:00 EST | 00:00 CST | 01:00 JST
Webinar Hightlights
The webinar covered
- iPSC-derived neurons with and without Transactive Response DNA-binding Protein mutations from ALS patients
- HD-MEA insights into functional changes, including hyperactivity and altered network dynamics in mutated neurons
- Foundational knowledge to advance targeted ALS treatment development
Agenda
Functional Characterization of Induced Pluripotent Stem Cells in Patients with Amyotrophic Lateral Sclerosis with Transactive Response DNA-binding Protein Mutation
Abstract
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by motor neuron degeneration leading to muscle weakness and eventual death. Early signs of ALS include muscle twitching, cramps, stiffness, and weakness. As the disease advances, individuals may experience slurred speech, difficulties chewing and swallowing, and, in some cases, cognitive decline. The primary aim of current therapies is to slow disease progression rather than restore neuronal function. To help pave the way for future therapeutic strategies, this study focused on understanding fundamental alterations in ALS neurons with TARDBP mutations. Using single-cell electrophysiology and high-density microelectrode arrays, we identified significant changes in firing rates, action potential activity, neuronal hyperactivity, and network dynamics in neurons derived from induced pluripotent stem cells (iPSCs) of patients with ALS and the TARDBP mutation compared to patients with ALS absent this mutation. These changes were particularly pronounced during neuronal stimulation and modulation by synaptic blockers. Our findings offer crucial insights into the pathological mechanisms of ALS motor neurons, helping to provide the foundational understanding necessary for development of targeted treatments.
