Translational Research to Advance Testing of Novel Drugs and Human Cell-Based Screening Platforms to Treat Pain and Opioid Use Disorder

Overview

The Research Need

New, safe interventions are needed to combat opioid misuse and addiction and to treat pain. Scientists need more accurate research models to understand how potential new drugs will affect humans, and they also must identify existing drugs or develop new therapies that could be effective treatments for pain and opioid misuse and addiction.

About the Program

Through the National Center for Advancing Translational Sciences (NCATS), NIH is providing a suite of translational science resources and technical expertise to investigators in the areas of pain, addiction, and overdose. These include:

  • Collaborations for Developing Drugs and Human Cell-Based Testing Platforms for Pain, Addiction, and Overdose
  • A Specialized Platform for Innovative Research Exploration (ASPIRE)
  • Tissue Chips to Model Nociception, Addiction, and Overdose

Program Details

To date, through the Helping to End Addiction Long-termSM Initiative, or NIH HEAL InitiativeSM, NIH has provided approximately $98.5 million to support 47 collaborative research projects, 22 prize awards, 5 research grants, and 3 supplements through the Translational Research to Advance Testing of Novel Drugs and Human Cell-Based Screening Platforms to Treat Pain and Opioid Use Disorder Program.

Research Examples

  • Pre-clinical testing of candidate therapeutics for the treatment of pain and opioid use disorder
  • Identification of potential therapies that work in novel ways assays (tests)
  • Development and high-throughput screening methods to test candidate therapeutics
  • Elucidation of promising chemical structures for therapeutic candidates

Collaborations for Developing Drugs and Human Cell-Based Testing Platforms for Pain, Addiction, and Overdose
This program fosters collaboration among pre-clinical researchers in the extramural community and experts at the NCATS intramural research program, Division of Preclinical Innovation, to advance knowledge about the underlying biology of pain, addiction, and overdose; develop new interventions to treat them; and determine which interventions are most effective. Collaborators bring a wealth of background knowledge and a starting point for a particular project, and NCATS scientists bring an equivalent wealth of knowledge in translation and the expertise to transform those starting points into useful tools and platforms for drug development.

A Specialized Platform for Innovative Research Exploration (ASPIRE)
The NCATS ASPIRE platform uses currently available knowledge to develop innovative artificial intelligence (AI) algorithms and predict and synthesize novel structures capable of interacting with specific targets; enable small-scale synthesis of the predicted molecules; and incorporate in-line, rapid biological testing of the molecules. Any new data obtained through this process would then be fed back into the system to further improve design, synthesis, and biological characteristics of molecules.

  1. ASPIRE Design Challenges to Develop Innovative and Catalytic Approaches Towards Solving the Opioid Crisis

The goal of the 2018 NCATS ASPIRE Design Challenges was to generate innovative and catalytic approaches toward solving the opioid crisis through the development of next-generation addiction-free analgesics with new chemistries, data-mining, and analytical tools and technologies, as well as biological assays that will revolutionize discovery, development, and pre-clinical testing of new and safer treatments for pain, opioid use disorder (OUD), and overdose. This prize competition was implemented through concurrent companion design challenges in these areas:

An event was held to recognize the 17 ASPIRE Design Challenges Winners on October 28, 2019. Winners were recognized for innovative approaches towards solving the opioid crisis and revolutionizing the discovery, development, and pre-clinical testing of next-generation, safer, and non-addictive analgesics to treat pain, as well as new treatments for OUD and overdose.

  1. NCATS ASPIRE Reduction-to-Practice Challenge

To further advance the NCATS ASPIRE Program and build on the innovations of the ASPIRE Design Challenges. NCATS issued a Reduction-to-Practice Challenge to prototype novel approaches that would lead to efficacious and non-addictive pain treatments and/or novel treatments for addiction and overdose and will be validated in the NCATS intramural ASPIRE facility. Winners* of the 2020 NCATS ASPIRE Reduction-to-Practice Challenge, (Stage 1: Planning Comprehensive Integrated Platforms) have been announced.

  • Iterative Learning and Automated Modular Platform for Optimum Nonaddictive Analgesic Discovery
  • Accelerating Molecular Innovation in Pain through an AI-Driven, Human-Guided, and Automated Open Drug Discovery Platform
  • Closed Loop Bio-Assay-Chemputer for Next Generation Analgesics (BioChemputer)
  • Development of a Comprehensive Integrated Platform for Translational Innovation in Pain, Opioid Abuse Disorder and Overdose
  • Biotech-in-a-Box, CDD’s Solution for Combating the Opioid Crisis

*According to the rules for these ASPIRE Design Challenges, non-U.S. citizens and non-permanent residents were not eligible to win a monetary prize (in whole or in part). However, their participation as part of a winning team was recognized above.

Tissue Chips to Model Nociception, Addiction, and Overdose

This initiative is creating human tissue-based microphysiological systems, also known as tissue chips or “organs-on-chips,” to understand the mechanisms underlying nociception (the nervous system’s response to painful stimuli), acute and chronic pain-relevant mechanisms, as well as addiction-, OUD-, and overdose-relevant mechanisms.

  • Tulane University – Louisiana
  • University of California, Los Angeles – California
  • University of Central Florida – Florida
  • University of Pittsburgh – Pennsylvania
  • University of Texas, Dallas – Texas

Funded Projects

2020
hiPSC-based DRG Tissue Mimics on Multi-well Microelectrode Arrays as a Tissue Chip Model of Acute and Chronic Nociception
Mar 19, 2020
2020
Human Microphysiological Model of Afferent Nociceptive Signaling
Mar 19, 2020
2020
Joint Pain on a Chip: Mechanistic Analysis, Therapeutic Targets, and an Empirical Strategy for Personalized Pain Management
Mar 19, 2020
2020
Multi-organ human-on-a-chip system to address overdose and acute and chronic efficacy and off-target toxicity
Mar 19, 2020
2020
TDCS TO DECREASE OPIOID RELAPSE
Mar 19, 2020

Closed Funding Opportunities

2019
HEAL Initiative: Announcement of the NCATS ASPIRE Design Challenges to Develop Innovative and Catalytic Approaches Towards Solving the Opioid Crisis
Sep 25, 2019