Development and Optimization of Non-Addictive Therapies to Treat Pain

Overview

The Research Need

More than 25 million Americans suffer from chronic pain, a highly debilitating medical condition that is complex and lacks effective treatments. Recent decades have seen an overreliance on opioids for the management of chronic pain despite their poor ability to manage chronic pain and improve the quality of life. Specifically, per the recent national health statistics report 22.1 percent of U.S. adults with chronic pain used a prescription opioid in the past 3 months (CDC.gov pdf  334.62 KB). This overreliance on opioids has contributed to a significant and alarming epidemic of opioid use disorders, overdose, and death. Therefore, the development of new non-addictive therapies for effective management of chronic pain as viable alternatives to opioids is urgently needed.

About the Program

This program supports the development and preclinical optimization of safe, effective, and non-addictive small-molecule and biologic therapeutics to treat pain. This research program includes optimization and early development of promising small molecules and biologic agents, studies that enable investigational new drug (IND) applications and culminate in Phase I clinical trials. The goal of the program is to accelerate the development of promising small-molecule and biologic leads toward clinical trials.

Researchers plan to develop novel pain relievers with improved specificity, fewer side effects, and low risks of misuse or dependency. This research will use in vitro assays and animal studies to advance multiple drug candidates. In the long term, the research will advance low-risk treatment options for chronic pain toward clinical development.

Open Funding Opportunities

2021
HEAL Initiative: Planning Studies for Initial Analgesic Development [Small Molecules and Biologics] (R61 Clinical Trial Not Allowed)
Jun 08, 2021
2022
HEAL Initiative: Team Research for Initial Translational Efforts in Non-addictive Analgesic Therapeutics Development [Small Molecules and Biologics] (U19 Clinical Trial Not Allowed)
Apr 22, 2022
2020
HEAL Initiative: Non-addictive Analgesic Therapeutics Development [Small Molecules and Biologics] to Treat Pain (UG3/UH3 Clinical Trial Optional)
Sep 16, 2020

Program Details

To date, through the Helping to End Addiction Long-termSM Initiative, or NIH HEAL InitiativeSM, NIH has funded 14 awards, three planning grants, one multidisciplinary team-based study and nine milestone-driven biphasic cooperative agreements totaling $32.3 million to research institutions and small businesses to support the development of non-addictive small molecules and biologic agents for the treatment of chronic pain. 

These research institutions and small businesses will undertake preclinical research and development that will provide new viable alternatives to opioids for treating pain. The projects will include collaborative, interdisciplinary team-science efforts as well as milestone driven focused studies with the goal of filing IND applications to the Food and Drug Administration for clinical exploration and commercialization.

Research Examples

Through their awards, the research organizations will develop and optimize non-addictive small molecules and biologic agents for the treatment of chronic pain.

The awardees will conduct research to:

  • Synthesize peripherally active Cannabinoid CB1 receptor agonists as analgesics.
  • Construct stem-cell loaded microgels to treat discogenic low back pain.
  • Profile the human gut microbiome for potential analgesic bacterial therapies.
  • Conduct site-directed RNA editing of Nav1.7 to block pain signals.
  • Target the cholecystokinin B receptor through a single chain fragment variable antibody.
  • Modulate pain signals through gene therapy for the carbonic anhydrase 8 gene.
  • Optimize a targeted central nervous system-penetrant small molecule to treat nerve pain.
  • Optimize a new MNK inhibitor to treat nerve pain.
  • Develop a safe, efficacious, and non-addictive small-molecule drug that activates Kv7 voltage-gated potassium channels to address overactive neuronal activity in diabetic neuropathic pain.
  • Test novel mGlu5 negative allosteric modulators as first-in-class non-addictive analgesic therapeutics in patients with a variety of chronic pain conditions.

  • 4e Therapeutics Inc. – Texas 
  • Cedars-Sinai Medical Center – California 
  • Centrexion Therapeutics – Pennsylvania  
  • Johns Hopkins University – University of Maryland 
  • Holobiome, Inc. – Massachusetts 
  • Knopp Biosciences, LLC – Pennsylvania 
  • Marine Biological Laboratory, Woods Hole – Massachusetts  
  • St. Louis College of Pharmacy – Missouri  
  • University of California at Davis – California 
  • University of Miami School of Medicine – Florida 
  • University of New Mexico Health Sciences Center – New Mexico 
  • Vanderbilt University – Tennessee 
  • Weill Medical College of Cornell University – New York 

Funded Projects

2021
Profiling the human gut microbiome for potential analgesic bacterial therapies
Sep 25, 2021
2021
Novel, non-opioid, non-addictive intrathecal therapy for the treatment of chronic pain
Sep 25, 2021
2021
Stem cell-loaded microgels to treat discogenic low back pain
Sep 25, 2021
2021
Disease Modifying Analgesia with CA8 Gene Therapy
Sep 25, 2021
2021
Site-directed RNA editing of Nav1.7 as a novel analgesic
Sep 25, 2021

Closed Funding Opportunities

2019
HEAL Initiative: Optimization of Non-addictive Therapies [Small Molecules and Biologics] to Treat Pain - (U44 Clinical Trial Not Allowed)
Sep 25, 2019
2019
Optimization of Non-addictive Therapies [Small Molecules and Biologics] to Treat Pain (UG3/UH3 Clinical Trial Not Allowed)
Sep 25, 2019