New developments in ALS and Alzheimer’s therapies

Oak Brook, IL – Volume 40 of SLAS Discovery includes four original research articles covering innovative screening platforms and assay technologies that accelerate drug discovery across neurodegenerative disease, transporter biology and challenging protein-protein interactions.

Original Research

• High-Throughput Screening of ALS Patient iPSC-Derived Spinal Motor Neurons Identifies Novel Compounds that Increase Neurofilament Light Chain Expression
  The authors engineer patient-derived induced pluripotent stem cells to generate spinal motor neurons, developing a high-throughput screening platform to screen over 6,000 compounds. l Novel candidates that increased neurofilament light chain expression in ALS (amyotrophic lateral sclerosis) models are identified and through subsequent investigations, the researchers identify a lead candidate that avoids TGF-β inhibition and demonstrates improved drug metabolism and pharmacokinetics. This approach yielded a promising new avenue for ALS therapy and highlights the utility of iPSC-derived neurons in disease modeling.

• A Versatile Acoustic Droplet Ejection Mass Spectrometry Platform Enables Drug Discovery for the Solute Carrier (SLC) Target Family
  This study establishes a high-throughput assay platform using acoustic ejection mass spectrometry that can quantify a broad range of substrates transported by solute carrier (SLC) proteins, a major class of drug targets. The platform was successfully validated across multiple SLC sub-families and scaled for hit identification in a pilot screening campaign against SGLT2, positioning it as a versatile, universal tool for discovering and characterizing SLC modulators.
• Development of a Nanobit-Based High-Throughput Screening Assay for Discovery of NOS1-NOS1AP Interaction Inhibitors
  Researchers develop and validate a nanobit-based luminescence complementation assay for high-throughput screening of inhibitors targeting the NOS1-NOS1AP protein-protein interaction—a pathway implicated in cardiovascular and neuropsychiatric disorders. By screening over 10,000 compounds, 19 validated hits are identified, including three with potent inhibitory activity, providing a reliable platform for discovering new therapeutics that disrupt this challenging target.
• Identification of a Small Molecule CAPON Binder Using Affinity Selection-Mass Spectrometry Screening
  The authors identify the first small-molecule binder for CAPON (NOS1AP), an adaptor protein linked to Alzheimer’s disease progression, using affinity selection–mass spectrometry to screen approximately 10,000 compounds. The lead compound, MA32, binds CAPON with a dissociation constant of 74 µM, revealing a druggable pocket on this previously unexplored target, providing a critical starting point for developing chemical probes and potential therapeutics.

Access to this volume of SLAS Discovery is available at https://www.slas-discovery.org/issue/S2472-5552(26)X2001-9

All active SLAS Discovery and SLAS Technology call for papers are available at: https://www.slas.org/publications/call-for-papers/

https://www.slas.org/publications/call-for-papers/

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SLAS Discovery reports how scientists develop and use novel technologies and/or approaches to provide and characterize computational, chemical and biological tools to understand and treat human disease. The journal focuses on drug discovery sciences with a strong record of scientific rigor and impact, reporting on research that:

• Enables and improves target validation
• Shares and/or compare novel methods for medium- or high-throughput screening
• Evaluates current drug discovery technologies
• Provides novel research tools
• Incorporates research approaches that enhance depth of knowledge and drug discovery success

SLAS (Society for Laboratory Automation and Screening) is an international professional society of academic, industry and government life sciences researchers and the developers and providers of laboratory automation technology. The SLAS mission is to bring together researchers in academia, industry and government to advance life sciences discovery and technology via education, knowledge exchange and global community building.

SLAS Discovery: Advancing the Science of Drug Discovery, 2025 Impact Factor 3.3. Editor-in-Chief Robert M. Campbell, PhD, Grove Biopharma, Inc., Chicago, IL (USA)

 

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