Translational Capabilities: Applying principles of pharmacology

Support quantitative systems pharmacology approaches that couple biological network and pathway analyses with mechanistic systems models and integrate data from disparate sources (e.g., preclinical and clinical; in vitro, ex vivo, in vivo; acute and chronic intervention) to enable predictive drug development. These efforts should:

  • encourage precompetitive academic-industry collaborations,
  • ensure full-transparency of data and analytical methods development, and
  • support cross-disciplinary training in all aspects of quantitative systems pharmacology, spanning experimental and clinical work to various types of modeling and simulation.

2030 RFA-AG-14-017: Planning Grants for Alzheimer's Disease Translational Centers for Predictive Drug Development (R34) RFA-AG-19-010: Alzheimer Centers for Discovery of New Medicines (U54) 4.G In Progress Support quantitative systems pharmacology approaches that couple biological network and pathway analyses… DN 2012 AD Summit: 2A and 2B 2018 AD Summit: 3J, 3K and 4F News: New NIH-funded translational research centers to speed, diversify Alzheimer’s drug discovery Blog: TREAT-AD centers: Open source tools to reinvigorate Alzheimer’s drug discovery Translational Tools, Infrastructure, and Capabilities TREAT AD Centers Emory-Sage-Structural Genomics Consortium (SGC)-Jackson Laboratory (JAX) TREAT-AD center Indiana University School of Medicine (IUSM)-Purdue TREAT-AD center 2014

  • Create a network of translational centers that will develop and apply the principles of quantitative and systems pharmacology to AD and ADRD drug development.

  • These centers will bring together expertise and technology needed for integration of multi-modal data analysis, mathematical modeling and empirical testing and apply a systems biology/systems pharmacology approach to the most challenging aspects in preclinical therapy development such as:

    1. therapeutic target selection and initial target validation,
    2. predictive toxicology,
    3. rigorous preclinical efficacy testing and development of translatable, preclinical biomarkers,
    4. comprehensive success and failure analyses,
    5. implementing precision medicine principles in clinical trial design.

    The centers will also provide training in all aspects of quantitative systems pharmacology, spanning experimental and clinical work to various types of modeling and simulation for the next generation of translational scientists.

Summary of Key Accomplishments

NIA launched two targeted funding initiatives that led to the establishment of four translational centers as part of the MODEL-AD and TREAT-AD Consortia, aimed at diversifying the therapeutic pipeline, accelerating therapy development, and enabling a precision medicine approach to drug development for AD. The Centers operate under open-science/open-source principles to ensure full transparency of data and analytical methods and unrestricted distribution of all research tools to researchers in the academic and industry sectors. The Centers are applying systems biology and systems pharmacology approaches to key aspects of drug development, such as therapeutic target selection and validation, rigorous preclinical efficacy testing, and the development of translatable, preclinical biomarkers.

The key accomplishments summary is current as of March 2022.