Launched in April 2018, the Helping to End Addiction Long-term (HEAL) Initiative is a trans-NIH effort to advance national priorities in addressing the opioid crisis. As part of the initiative, NIH developed a research plan to bolster research to enhance pain management strategies and improve treatments for opioid misuse and addiction.
More than 2 million Americans have an opioid use disorder, and even more misuse these medicines by taking them longer or in higher doses than prescribed.1 To address the opioid epidemic, new, safe interventions are needed to combat opioid misuse and addiction and to treat pain. Not only are more accurate research models needed to understand how potential new drugs will affect humans, but scientists also must identify existing drugs or develop new therapies that have potential as effective treatments for opioid misuse and addiction and for pain.
NCATS Role in HEAL
As part of HEAL, NCATS will accelerate the process of developing new treatments for opioid misuse and addiction and for pain. Because NCATS focuses on translational science — through which new interventions are developed, demonstrated and disseminated to improve human health — the Center is poised to address the public health crisis of opioid use in unique ways.
NCATS is leading trans-NIH collaborative HEAL efforts to:
- Develop new testing platforms that more closely model human biology than currently available cell and animal models, using induced pluripotent stem cells (iPSCs), tissue chips and 3-D tissue bioprinting;
- Identify and de-risk potential drugs that work in novel ways through development of assays (tests), high-throughput screening and optimization of promising compounds; and
- Advance promising new drug candidates through rigorous pre-clinical efficacy and safety studies for first-in-human clinical trials as required by the Food and Drug Administration (FDA).
NCATS is providing a suite of translational science resources and expertise to the research community working on opioid and pain research. With this expert collaborative infrastructure already in place, NCATS will accelerate the process of getting new treatments for pain and for opioid misuse and addiction to patients faster.
NCATS-Supported HEAL Projects
NCATS currently supports one HEAL-related project.2 The Human Cell-Based Screening (HCBS) Platforms and Novel Drugs to Treat Pain, Addiction and Overdose project has two components:
- HCBS platform development and
- Identifying and optimizing promising compounds for Investigational New Drug (IND)-ready therapies.
HCBS Platform Development
NCATS will focus on creating human cell-based models of opioid misuse and addiction and of pain. Through the following three initiatives, NCATS-supported researchers will develop models at the cell, tissue and integrated systems levels. The goal is to develop accurate research models that reflect the complexity of human biology and better predict how potential new drugs will affect humans.
iPSC-Derived Neurons for Pain, Addiction and Overdose
Scientists in NCATS’ Stem Cell Translation Laboratory (SCTL) will develop a renewable supply of human cell-based models, focusing on patient-derived iPSC lines that give rise to specialized, functional nerve cells that are relevant for opioid misuse and addiction and for pain. NCATS will offer robotic manufacturing of validated and quality-controlled human cells to leverage diverse research projects that the Center conducts or supports. NCATS’ Division of Pre-Clinical Innovation will provide access to iPSC lines, iPSC-derived cell types, protocols, cutting-edge technologies and multidisciplinary scientific expertise.
3-D Bioprinted Tissue Models
Experts in NCATS’ 3-D Tissue Bioprinting program will develop complex human, biologically relevant, 3-D tissue-in-a-well models of addiction, pain and the blood-brain barrier for high-throughput drug screening using bioprinting techniques, iPSC-derived neurons and other cells supplied by the SCTL. Collaborators will have access to NCATS’ research resources.
Dorsal Root Ganglion and Brain Tissue Chip
The dorsal root ganglion is a part of the nervous system that translates pain. Blood vessels that support the nervous system have a filtering mechanism that blocks the passage of many substances. This blood-brain barrier prevents many potential drugs from reaching the nervous system. To help overcome this obstacle, NCATS-supported scientists will develop a biologically relevant, human tissue-based, 3-D model of the pain pathway that will be useful for the evaluation of potential therapeutics, as well as models for opioid misuse and addiction.
Identifying and Optimizing Promising Compounds Toward IND-Ready Therapies
Using the Center’s therapeutic development resources, NCATS scientists will collaborate with the external research and development community as well as other scientists at NIH to identify existing and potential new drugs for pre-clinical development. The following three initiatives will focus on accelerating the testing needed to bring promising drug candidates to first-in-human studies.
Probe/Drug Lead Production
Working collaboratively with research experts in opioid misuse and addiction and in pain, NCATS will identify drug-like compounds that act on biological targets of opioids and pain, then test these in cell- and animal-based models. Available collaborative resources include compound libraries, high-throughput screening, test validation, informatics tools and medicinal chemistry. The libraries also will leverage repositories of natural products available through the National Cancer Institute and the Fogarty International Center.
New Chemical Structures for Pain, Addiction and Overdose Targets
Through A Specialized Platform for Innovative Research Exploration (ASPIRE), NCATS scientists will design and build new chemical structures to combat opioid misuse and addiction and treat pain. NCATS will integrate automated synthetic chemistry (ASC), artificial intelligence and biological testing into a modular platform. The goal is to build fully automated technology for collaborative research projects conducted by or supported through NCATS. Using this platform, scientists will apply new ASC techniques and testing capabilities to accelerate the development of new therapeutics.
ASPIRE also will support the development of new chemistries, biological assays, data-mining tools and other analysis technologies through a challenge competition for integration into the ASPIRE platform. Research challenge prizes will be offered in the areas of a database, an electronic laboratory knowledge portal, machine learning algorithms and biological assays. An additional challenge will focus on a combined solution for two or more areas.
Clinical Candidate IND Application Production
Scientists in NCATS’ Pre-Clinical Therapeutics Development Branch, including those in the Therapeutics for Rare and Neglected Diseases and Bridging Interventional Development Gaps programs, will identify and optimize new drug candidates for opioid misuse and addiction and for pain. Researchers will determine which candidates can be further developed and tested to enable IND applications to the FDA and subsequent early-phase testing in humans. Available resources include medicinal chemistry, pharmacology, testing of the metabolic properties of compounds, compound safety profiles, optimal drug formulation for administration in humans, and manufacturing methods to produce sufficient quantities of potential drugs for pre-clinical and clinical evaluation.
1.NIH HEAL Initiative Research Plan
2.More HEAL projects will be added as they are announced.