Don’t miss our upcoming webinar on stem cell-based pain and CNS drug discovery. Attendees can gain knowledge of compound profiling to advance research in the CNS and pain therapeutic fields and get an understanding of the principles of operation of Cellectricon’s phenotypic screening platform.
Speakers:
Paul Karila, VP of Discovery Services, Cellectricon
Ashley Barnes, Head of Drug Discovery Services, Censo Biotechnologies
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Abstract:
Physiologically relevant human models of chronic pain are essential to developing new therapeutics and overcome poor translation between animal studies and the clinical setting. In this webinar, we will describe the development of sensory neurons derived from induced pluripotent stem cells (iPSCs) with a relevant phenotype and how these cells can be applied in screening to identify compounds that change a disease phenotype rather than the activity of specific targets.
The approach is based on using sensory neurons derived from well-characterised iPSCs produced by Censo combined with Cellectricon’s unique screening technologies, IP and know-how. By utilizing human iPSC-derived sensory neurons and a physiological stimulus (electric field stimulation; EFS) in combination with calcium imaging in a high capacity format, we can detect changes in neuronal excitability in a screening setting. The iPSC-derived neurons express key gene and protein markers of sensory neural development and specific, pain-relevant targets and are well-adapted to screening in 384-well format.
We demonstrate that the approach has a translational predictability and present data on clinically used drugs (e.g. gabapentin and naproxen) as well as tool compounds such as novel sodium channel inhibitors. There is a good agreement between inhibition of excitability as measured by EFS in human iPSC-derived sensory neurons and effect in the clinic as well as conventional methods in human dorsal root ganglion neurons.
The results show the advantage of using a phenotypic screening platform in conjunction with high quality human iPSC-derived sensory neurons to provide a higher-throughput means of quantifying the excitability of human neurons whilst maintaining the translational validity. This platform enables the identification and prioritization of novel molecules that are likely to modulate chronic pain earlier on in the drug development process.
The attendees will:
- Learn about phenotypic screening approaches in pain research and how iPSC-derived neurons can be used in drug discovery.
- Gain knowledge of compound profiling to advance research in the CNS and pain therapeutic fields.
- Gain insight into sourcing and production of high quality iPSC-derived sensory neurons.
- Get an understanding of the principles of the humanized phenotypic screening platform and how it can be applied for stem cell-based screening against disease-relevant phenotypes.
Presented by:
Paul Karila, PhD, VP of Discovery Services, Cellectricon
Paul is responsible for building and providing discovery services at Cellectricon’s labs in Mölndal, Sweden employing excitable native and stem cell models. Paul joined Cellectricon from AstraZeneca (AZ) where he held leadership positions at the Departments of Molecular Pharmacology and Neuroscience. Paul led teams responsible for ion channel and GPCR profiling in LI-LO phase, mainly on analgesia targets. Prior to joining AZ, Paul was a Postdoctoral Fellow at School of Medicine, University of Pittsburgh, PA, USA studying neurobiology using electrophysiological methods. Paul earned his PhD at the University of Gothenburg, Sweden in 1997.
Ashley Barnes, Head of Drug Discovery Services, Censo Biotechnologies
Ashley is responsible for leading the drug discovery service group in Babraham, Cambridge, UK. He joined Censo in 2016 following 21 years at GlaxoSmithKline. Ashley has extensive experience in drug discovery including target validation, screening and assay development. He has disease and programme leadership expertise in neuroscience, respiratory, and inflammation.