Funded Projects

More than 700,000 total knee replacement surgeries are performed each year in the United States to relieve joint pain in patients with end-stage osteoarthritis or rheumatic arthritis. However, many patients still experience significant pain after this procedure, calling for additional long-lasting, drug-free pain management strategies. This project will develop and test a commercial prototype device for persistent knee pain after total knee replacement. The injection-based method freezes peripheral nerves to reduce pain sensation.

A critical line of defense against opioid use disorder (OUD), one of the nation’s leading preventable causes of death, must be standardized screening provided by the patient’s primary care physician, psychiatrist, and/or counselor. Standardized screening methods for opioids, however, are simply inferior and no gold standards exist. This project aims to develop a validated, theoretically guided tool that provides clinicians with information beyond OUD symptoms using reinforcer pathology, a measure of severity derived from the synergy between excessive delay discounting and high behavioral economic demand. The Behavioral Economic Screening Tool (BEST-OUD) will use these combined measures in a mobile tablet application to enable clinicians to screen for OUD.

While the mu opioid receptor (MOR) antagonist naloxone has proven invaluable as an opioid overdose antidote, naloxone suffers from a very short duration of action (half-life is approximately 1 hour) and has been found to be less effective against newer, long-acting opioids, including fentanyl (half-life is approximately 7–10 hours). This leads to a highly lethal and increasingly prevalent phenomenon known as “renarcotization,” wherein an overdose patient revived with naloxone can re-enter an overdose state from residual fentanyl in the body. Thus, there is a critical need to develop a long-acting MOR antagonist formulation that can address renarcotization by providing multi-hour protection. The goal of this project is to reformulate naloxone using FDA-approved microencapsulation technology into a long-acting injectable (LAI) that can provide 12–24 hours of sustained antagonist activity in vivo. It will employ a proprietary Computational Drug Delivery™ software, called ADSR™, to perform in silico formulation optimization as well as to predict its in vitro dissolution and in vivo pharmacokinetic behavior.

Most of the 200k Americans who undergo thoracotomy each year receive opiates to reduce postoperative pain because clinicians have few non-addictive, cost-effective choices to control the severe pain patients often experience in the first two weeks after surgery. Managing pain post-thoracotomy is critical to enable patients to take deep breaths and remove (via coughing) lung secretions that otherwise significantly increase risk of pneumonia and collapsed lung, hospital re-admission and morbidity. The most severe pain associated with thoracotomy is transmitted along the intercostal nerves, but no long-term analgesic or nerve block device exists that can provide safe and effective long-term reduction of pain. A reversible, patient-controlled, non- addictive, intercostal nerve block device would reduce suffering due to thoracotomy, broken ribs and herpes zoster. In this Phase I project, the team will develop a minimally invasive thermal nerve block device that can control nerve conduction by gently warming and cooling a short nerve segment between room temperature and warm water temperature. This novel approach is based on the discovery that warm and cool temperature mechanisms of nerve block are different and additive, enabling moderate-temperature nerve block by cycling neural tissues slightly above and below body temperature. Reversible thermal nerve blocks represent a completely new approach to managing pain.  

The need to develop non-opioid therapeutics for chronic pain is greater than ever.  One option being explored is inhibiting the activity of calpains – enzymes that have been shown to cause pain in animal models of chronic pain.  Using an artificial intelligence (AI)-driven drug discovery platform, researchers have uncovered and validated four calpain-1 inhibitors using biochemical assays.  This study by 1910 Genetics Inc. hopes to synthesize multiple analogs of its most potent discovered calpain-1 inhibitor and determine its effectiveness against calpain-2 and certain enzymes that break down proteins.  Findings that successfully significantly inhibit calpain-1 in at least one animal model of chronic pain could lead to the first oral, central nervous system penetrating selective calpain-1 inhibitor [non-opioid therapeutic] for chronic pain.

Nerve stimulators are devices surgically implanted near a peripheral nerve or on the spinal cord that use electrical signals to reduce the perception of pain. Although these devices can provide effective pain relief to patients, many have high complication rates, resulting from the wire moving, breaking, not working, or the implantable battery pack or permanent wire causing new pain. This project will support the development and animal testing of a peripheral nerve stimulator to treat chronic pain which can be implanted without surgery. Once injected, the device will provide pain relief through electrical stimulation and then be safely degraded and resorbed by the body.

 Investigating the broader efficacy of sEH inhibition and specifically our IND candidate, EC5026, has indicated that it is efficacious against chemotherapy induced peripheral neuropathy (CIPN). This painful neuropathy develops from chemotherapy treatment, is notoriously difficult to treat, and can lead to discontinuation of life-prolonging cancer treatments. Thus, new therapeutic approaches are urgently needed. The research team will investigate if EC5026 has potential drug-drug interaction with approved chemotherapeutics or alters immune cells function, and assess the effects of sEHI on the lipid metabolome and probe for changes in endoplasmic reticulum stress and axonal outgrowth in neurons. The team proposes to more fully characterize the analgesic potential of our compound and investigate on and off target actions in CIPN models and model systems relevant to cancer therapy.

Even though pain is a nearly universal experience, objective measurements of pain remain difficult. Given that responding to the opioid crisis will require both better ways to manage pain and better ways to detect drug-seeking behavior, finding approaches to objectively measure pain is crucial. The goal of this project is to develop a product that will objectively measure pain using computer vision and machine learning technologies together with tablet-based self-reported pain data from patients for research or clinical purposes. The product will be low cost, involving one or two cameras to record the video and a computer to analyze the video in almost-real time, and will involve software that can be portable to ordinary personal computers and tablets. The project will capture facial expressions related to genuine pain and integrate it with patients’ self-reported pain data, in order to refine the product and create an objective measure of pain intensity that can be used in clinical settings and test its accuracy. This new tool has the potential to help rectify the poor pain outcomes that still plague Americans with opioid addiction, cancer, and other health conditions in many health care settings.

One of the most widely used treatments for chronic pain is opioid analgesics. Importantly, there is evidence of a pathological interaction between opioids and the immune system that can contribute to both opioid tolerance and elevated levels of pain. Chronic pain conditions for which opioids are most often prescribed have been shown to involve dysregulation of the immune system, which may contribute to pathological effects of opioid use in these patients. To address this unmet need, this study aims to develop a reliable, cost-effective, and non-invasive in vitro diagnostic assay for chronic pain with an underlying inflammatory pathology, as a blood test available in primary care settings, with the hope that doctors can use the test to identify which patients might benefit less from opioids and be more likely to become addicted.

Rescue of victims of opioid overdose is accomplished by treatment with antagonist drugs, such as naloxone, that can reverse the respiratory depression. However, naloxone has serious liver toxicity and a short half-life, and its complete antagonism results in a withdrawal effect. Nalmefene is an FDA-approved opioid derivative that is an antagonist of the MOR and a weak agonist of the k-opioid receptors (KOR). An immediate release intravenous injectable formulation was approved by the FDA in 1995 for opioid overdose; however, the requirement for intravenous administration has limited its clinical use. This project, in partnership with Avior, aims to develop a fast-onset, rapidly-dissolving, mucoadhesive thin film formulation that carries uniformly distributed nalmefene nanoparticles on the surface of the film. This film, produced using Avior’s proprietary Speedit™ transmucosal drug delivery technology, rapidly delivers nalmefene when the film is placed in contact with the lower lining of the inner lip. This project will generate non-clinical data to support critical human clinical trials to determine if a transmucosal film can be developed with a rapid onset of action that is required for rescue of opioid overdose patients or taken prophylactically to prevent respiratory depression, to assess whether the effective speed of delivery is sufficient to conduct a human clinical trial.

While effective treatments exist for substance use disorders, adhering to treatment and retaining patients in treatment can be a challenge. The objectives of this project are to facilitate the implementation of loyalty/reward-based programs to increase adherence to medical treatment among patients with substance use disorders through innovative solutions to common challenges. Building on experience developing software to promote patient appointment attendance, the project will build a new tool to test on a sample of 10 providers and 10 patients who are prescribed but not fully adherent to substance use disorder treatment. Patients will receive tailored text messages (in English or Spanish) encouraging adherence, self-report their treatment adherence (which will be verified through smart pill caps and biological testing), earn points for adherence that can be exchanged for rewards customized for them based on a baseline survey, and report their satisfaction with the program and process at the end of the 4-week study. This pilot will assess the feasibility and perceived usefulness of the product in support of eventual larger-scale testing in a clinical trial.

Chronic pain affects more than 100 million adults in the United States, resulting in disability, loss of work productivity, and overall reductions in health, making chronic pain a major public health problem with an economic burden estimated at $560–635 billion annually. Opioids, the most frequently prescribed class of drugs to control pain, lack evidence supporting their long-term efficacy and carry a 15% to 26% risk of misuse and abuse among pain patients. Guided imagery (GI) is an effective non-pharmacological intervention for reducing pain, but its effectiveness is limited by patients’ imaging abilities. This project will develop and assess the feasibility of an at-home virtual reality system, Limbix VR Kit, to reduce chronic pain and opioid reliance, as well as improve other functional outcomes, by delivering an immersive GI experience.