Phenotyping of Human iPSC-derived Neurons: Patient-Driven Research

Phenotyping Human iPSC-derived Neurons: Patient-Driven Research examines the steps in a preclinical pipeline that utilizes iPSC-derived neuronal technology, also providing considerations and best practices. By using example projects in ALS and epilepsy as a template, the text allows readers to understand what considerations are important to assess at the start of project design. The book addresses reproducibility issues at each stage of the pipeline and provides suggestions for improvement. From patient sample collection and proper controls to neuronal differentiation, phenotyping and screening, these detailed descriptions of each stage of the pipeline will help everyone, regardless of stage in the pipeline. In recent years, drug discovery in the neurosciences has struggled to identify novel therapeutics for patients with varying indications, including epilepsy, chronic pain and psychosis. Current treatment options for such patients are decades old and offer little relief with many side-effects. One explanation for this lull in novel therapeutics is a lack of novel target identification for neurological disorders (and target identification requires exemplar preclinical data). To improve on the preclinical work that often relies on rodent modeling, the field has begun utilizing patient-derived induced pluripotent stem cells (iPSCs) to differentiate neurons in vitro for preclinical characterization of neurological disease and target identification.  Discusses techniques and new technology for iPSC culturing and neuronal differentiation to establish best practices in the lab Outlines considerations for phenotypic assay development Provides information about the successes, failures and implications of screening with iPSC-derived neurons INDICE: 1. iPSC culture: best practices. From sample procurement, to iPSC reprogramming, proper controls (including CRISPR), other iPSC considerations2. Development of transcription factor (TF)-based neuronal differentiation protocols3. Utilizing patterning-based differentiation protocols to generate mixed populations of neuronal subtypes for more physiologically relevant disease modelling of Angelman Disorder4. Optimizing differentiation of support cells5. Limitations of iPSC-derived neurons for the study of neurodegeneration Utilizing patient-derived neurons to develop a pipeline for studying early onset psychosis6. How iPSC-derived neurons can be used to further patient-specific therapeutics for pain and neuropathy7. Using monogenic-defined ASD to better understand idiopathic ASD8. Understanding the limitations of neuronal phenotyping. The advantages and disadvantages of organoids in a drug discovery pipeline9. Considerations for assay development - a case study with ALS-derived patient neurons10. Scaling up neuronal differentiations for screening11. Selection libraries for screening on iPSC-derived neuronsWhen and how should automation be introduced in the iPSC-derived neuronal disease modelling pipeline? (NCATS)12. High-throughput screening with iPSC-derived neurons from 2-dimensional cultures13. Screening with iPSC-derived neurons from 3-dimensional cultures14. How can iPSC-derived neuronal work move into the clinic?

• ISBN: 978-0-12-822277-5
• Editorial: Academic Press
• Encuadernacion: Rústica
• Páginas: 350
• Fecha Publicación: 01/11/2022
• Nº Volúmenes: 1
• Idioma: Inglés