Developing Drugs and Human Cell-Based Testing Platforms for Pain, Addiction and Overdose
Safe, effective, and non-addictive drugs (small molecules and biologics) to treat pain, mitigate addiction and reverse overdose are key to addressing the opioid crisis. Given the limitations of current treatments and failures in development efforts for new therapies, drugs with better activity profiles that modulate novel targets, and more predictive drug development platforms, are needed. The NIH Helping to End Addiction Long-termSM (HEAL) Initiative is a trans-NIH effort launched in April 2018 to advance national priorities in addressing the opioid crisis through science. The NCATS-led, HEAL Human Cell-Based Screening Platforms and Novel Drugs to Treat Pain, Addiction and Overdose (HCBS) initiative is a multi-component collaborative program that will develop human-based, physiologically relevant in vitro screening and characterization systems, high efficiency synthesis and testing of small molecule compounds to modulate novel pain, addiction, and overdose targets, and investigational new drug (IND)-enabling studies for drugs for these indications.
The NCATS Division of Pre-Clinical Innovation (DPI), the intramural component of NCATS, comprises industry-scale expertise in stem cell biology, assay development, biomolecular screening, automated biology, medicinal chemistry, cheminformatics, data science, and pre-clinical drug development, with advanced equipment and resources not available in most laboratories, such as large compound libraries (e.g., diverse drug-like molecules, approved and investigational drugs, mechanism-based compounds, and natural products); quantitative high-throughput and high-content screening; robotic automated cell culture; multiscale assay development; 3-D bioprinting; next-generation DNA and RNA sequencing, and integrated platforms to profile gene and protein expression and measure functional endpoints in cell cultures, and on single-cells.
Every NCATS DPI project is a collaboration with an external partner in the academic, biopharmaceutical, or nonprofit sector. DPI functions via a unique operational model which takes advantage of the complementary nature of NCATS’ translational expertise and collaborators’ biology/target/disease expertise. Collaborators bring a wealth of background knowledge and a starting point for a particular translational project, and NCATS scientists bring an equivalent wealth of knowledge in translation and the expertise to transform those starting points into therapeutically useful tools, platforms, or investigational drugs. Joint project teams design and follow milestone-driven project plans to achieve pre-agreed to deliverables specific to the need and stage of the project. Projects are provided the needed resources as long as milestones and timelines continue to be met, until the pre-agreed to deliverables are achieved. At whatever stage the projects conclude, the joint teams publish results in scientific journals where appropriate, and disseminate relevant data, protocols, and materials.