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Creative Biolabs

ALS High-Throughput Phenotypic Screening Assay Service

Amyotrophic lateral sclerosis (ALS) remains a devastating enigma. Its intricate pathogenesis, still not yet fully understood, defies conventional drug development approaches. Traditional methods, tethered to pre-defined targets, often fall short in capturing the disease's multifaceted nature. Our ALS high-throughput phenotypic screening service shatters these limitations. We leverage a powerful, target-agnostic strategy, allowing you to explore the vast landscape of cellular responses to potential therapeutics. By observing how compounds influence complex ALS-relevant phenotypes, we unlock novel targets and mechanisms of action previously hidden from view. For further information regarding the products and services provided, project-specific consultation, and pricing, please submit an inquiry here.

ALS Patient-Specific Cell Models

  • iPSC-Derived Motor Neurons

We utilize induced pluripotent stem cells (iPSCs) derived directly from patients carrying well-characterized ALS-associated gene mutations, including SOD1, C9orf72, and FUS. These iPSCs are differentiated into motor neurons, providing a physiologically relevant platform to model familial ALS pathogenesis. This model is ideal for high-throughput drug screening, enabling the identification of compounds that specifically target genetic subtypes of ALS.

Fig.1: iPSC-derived motor neuron representative images. Fig.1 Representative images of iPSC-derived motor neurons.1, 3

  • Sporadic ALS Fibroblasts

We employ fibroblasts from patients with sporadic ALS, those without known genetic mutations, to capture the broader spectrum of the disease. Utilizing high-content imaging with markers such as EEA1 and FUS, we perform detailed phenotypic characterization of these cells. This allows us to identify subpopulations exhibiting dysregulation of key pathways, such as the FUS-ALS pathway, providing critical insights into the underlying disease mechanisms.

Advanced Imaging and Automation Assays

  • Live-Cell Dynamic Imaging

We employ fluorescent probes to capture real-time neuronal calcium signaling, enabling the visualization and quantification of critical ALS phenotypes, such as excitotoxicity. This dynamic imaging approach provides a window into the functional changes occurring in ALS neurons, revealing subtle yet crucial alterations.

  • Multi-Dimensional Phenotypic Analysis

Our high-content imaging (HCI) platform allows for the simultaneous monitoring of multiple phenotypic parameters, including cell morphology, activity, and secretion. This multi-parametric analysis unveils the intricate complexity of ALS excitatory phenotypes, providing a comprehensive understanding of disease mechanisms. This system allows for the finding of compounds that can correct multiple disease parameters at once. This comprehensive view enables the identification of compounds that effectively address the multifaceted nature of ALS.

Case Study: Human iPSC-derived motor neurons exhibit electrophysiological functions, and ALS motor neurons demonstrate hyperexcitability.

Fig.2: Using iPSC-derived motor neurons to assess ALS neuronal activity and overstimulation. Fig.2 Evaluation of ALS neuronal activity and overstimulation using iPSC-derived motor neurons.2, 3

Our comprehensive ALS high-throughput phenotypic screening service integrates state-of-the-art technology with the expertise of our dedicated scientific team, propelling your drug development efforts forward. We offer a powerful combination of precise cellular phenotyping and multi-dimensional analysis, delivering efficient and reliable screening solutions tailored to your research needs. Please contact us for customized solutions!

References

  1. Phatnani, Hemali, et al. "An integrated multi-omic analysis of iPSC-derived motor neurons from C9ORF72 ALS patients." Iscience 24.11 (2021).
  2. Kondo, Tosho, et al. "Rapid and robust multi-phenotypic assay system for ALS using human iPS cells with mutations in causative genes." International journal of molecular sciences 24.8 (2023): 6987.
  3. Distributed under Open Access license CC BY 4.0, without modification.
For Research Use Only. Not For Clinical Use.
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