Funded Projects

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.

The use of a pain imaging technology would allow for objective efficacy data (both pre-clinically and in clinical trials), and reduce costs by enabling smaller sample sizes due to more homogeneous populations; i.e. with a particular “pain signal,” and more accurate measurement of analgesic effects. This research team recently invented a novel positron emission tomography (PET) imaging agent as a tool to address these issues in pain care and therapy development. Although the ability of PET to detect pathological changes for (early) disease detection is widely used in cancer and neurological diseases, it has not yet been used for pain indications. The goals of this project are: 1) to change the evaluation of (experimental) pain therapies, and 2) the standard of care in pain assessment through molecular imaging. The proposed study is designed to determine the feasibility of our imaging agent to objectively measure pain in rodents. This will set the stage for a Phase II study that further develops this agent into a tool for quantifying pain/analgesia.

Noninvasive brain stimulation (NIBS) may be effective in treating some forms of addiction, but the most common NIBS methods, Transcranial Magnetic Stimulation (TMS) and Transcranial Direct Current Stimulation (tDCS), have not been found to be effective in treating opioid use disorder (OUD). This project seeks to test the efficacy in OUD patients of Electrosonic Stimulation (ESStim™), an improved NIBS modality that combines independently controlled electromagnetic and ultrasonic fields to focus and boost stimulation currents via tuned electromechanical coupling in neural tissue.

Sober Grid™ has developed a smartphone-based mobile application currently in use by more than 120,000 individuals worldwide who are in, or seeking, recovery from drug and alcohol addiction. The “Grid,” as it is known, is a mobile-based, social recovery community providing rapid context-specific peer support, efficient help seeking, motivational enhancement exercises, and member ratings of support content—all aimed to prevent relapse. The overarching goal of this phase II project is to extend the current capabilities of the Sober Grid app to achieve a comprehensive social recovery support app featuring intelligent, context-appropriate resource matching and 24/7 rapid-response peer coaching that is effective in reducing disordered substance use and is cost-effective. This projects tests whether providing this functionality to high-risk members will be acceptable, feasible, increase access to and engagement with resources, and have a positive effect in increasing time to relapse and days of consecutive abstinence.

This project, a partnership with Principled Strategies, will develop innovative, patient-level models for opioid risk identification and integrate them into the SafeUseNow managed care system—an actionable solution for combating prescription drug abuse that currently operates at the prescriber level only. Incorporating patient-level risk identifier models will strengthen an already powerful and demonstrably effective program and constitutes a critical step in generating a first-in-class, multifactor risk assessment strategy that is truly holistic. Using a variety of data sources, advanced analytics, and multiple empirically validated risk identification models, the groundbreaking advancement in SafeUseNow technology will enable health care stakeholders to identify combinations of prescribers, patients, and pharmacies whose behaviors may contribute to prescription drug abuse. This project will work to obtain new datasets for analysis, assess them, and use them to build national patient-level risk models for relevant outcomes, which will enable the development and evaluation of a next-generation prototype for a patient-level version of SafeUseNow.

As the opioid crisis claims more and more lives, there is a need to develop new, safer analgesics. Biased agonists could activate beneficial signaling pathways while avoiding those that cause adverse effects. This project aims to speed the discovery of non-addictive analgesics by providing drug discovery teams with simpler, more robust, more quantitative assays for agonist bias. The goal is to optimize and test new assays for agonist bias at NOP, D3 dopamine, CB1 cannabinoid, and OPRM1 opioid receptors, which couple to both the Gi and ?-arrestin signaling pathway, and create new tools to improve the analysis of structure/activity relationships that can be used in drug discovery and distribute to researchers who are developing new drugs for OUD.

Analgesia for post-operative populations remains a significant health need that calls for innovative therapies which improve both safety and outcome measures. Recent FDA drug safety warnings and studies focusing on post-operative analgesia have highlighted the imperative need for new approaches that can be utilized for common clinical scenarios. Accordingly, novel treatment options that are safe and afford additional benefit in relief of pain are needed. In this proposal, the development of an innovative surgical sealant technology is proposed that functions at the level of the surgical wound bed and actively delivers local pharmacologic agents to therapeutically address post-operative pain. New formulations of several analgesic regimens will be assessed for their ability to seal wounds and provide appropriate pain management.

For many individuals in recovery from a substance use disorder, certain cues—including stress and drug-related cues—can trigger a physiological state in which they are more likely to relapse. In this SBIR project, the investigators intend to deploy a system—consisting of a wearable sensor, a smartphone app, and a clinical portal—to provide individuals in recovery and their treatment providers with an opportunity to identify moments of high risk for relapse and to access real-time intervention opportunities. The sensors will identify signals of stress or drug use, interface with a smartphone app, and provide options for annotations, stress-reduction techniques, or contact with an individual’s support system and treatment providers, as well as log and encourage healthy behaviors. This study will deploy and optimize the system, as well as test its effects on addiction-related outcomes, such as rate of relapse.

Adolescents face increased HIV risk, infrequent testing, inconsistent linkage to care, and a lack of prevention-related knowledge. We propose to complete and evaluate the Mobile Augmented Screening (MAS) tool to privately and discretely offer routine HIV testing and counseling, including prevention education, to high-need, diverse adolescent and young adult populations at a low cost. The MAS will consist of a tablet-based intervention including a brief video designed to increase adolescent HIV testing, automated text messages to facilitate linkage to care for those who test positive, and text-based education for those who test negative or decline testing. Phase I was conducted with young emergency department (ED) patients. Preliminary evaluations indicate the video led to significant knowledge increases and encouraged testing. In phase II, we seek to complete intervention development and evaluate through a randomized controlled trial with ED patients, with qualitative interviews for a subset of young patients and ED staff.

Maternal use and addiction to opioids or other drugs has resulted in an unprecedented rise in drug withdrawal complications in newborns known as neonatal abstinence syndrome (NAS). While there is no accepted standard for treating NAS, non-pharmacological bundles are recommended as an initial course of treatment. Unfortunately, non-pharmacological care (swaddling, rocking, frequent feedings, and skin contact) require significant use of human resources. This project studies the technical feasibility of a stochastic vibrotactile stimulation (SVS) technology incorporated into the hospital bassinet pad, which provides gentle vibrating sensory stimulation to soothe infants with NAS. Building on preliminary evidence that this type of stimulation calms NAS infants without altering their sleep, this study aims to develop a commercially viable bassinet pad that could be used in a hospital setting.

 Non-Invasive Brain Stimulation (NIBS) has been successfully applied for the treatment of chronic pain (CP) in some disease states, where treatment induced changes in brain activity revert maladaptive plasticity associated with the perception/sensation of CP [25-28]. However, the most common NIBS methods, e.g., transcranial direct current stimulation, have shown limited, if any, efficacy in treating neuropathic pain. It has been postulated that limitations in conventional NIBS techniques’ focality, penetration, and targeting control limit their therapeutic efficacy . Electrosonic Stimulation (ESStim™) is an improved NIBS modality that overcomes the limitations of other technologies by combining independently controlled electromagnetic and ultrasonic fields to focus and boost stimulation currents via tuned electromechanical coupling in neural tissue . This proposal is focused on evaluating whether our noninvasive ESStim system can effectively treat CP in carpal tunnel syndrome (CTS), both as a lone treatment and in conjunction with physical therapy (PT). Investigators hypothesize ESStim can be provided synergistically with PT, as both can encourage plasticity-dependent changes which could maximally improve a CTS patient’s pain free mobility. In parallel with the CTS treatments, the team will build multivariate linear and generalized linear regression models to predict the CTS patient outcomes related to pain, physical function, and psychosocial assessments as a function of baseline disease characteristics. The computational work will be used to develop an optimized CTS ESStim dosing model. 

With nearly 116 million people suffering from chronic pain in the United States, there is a need for new analgesics without the risks posed by opioids. Antagonists acting at TRPV1 receptor have long been recognized as one of the most promising novel classes of non-opioid analgesics. Initial tests in humans have confirmed that this class of drugs produces analgesia and is safe and well-tolerated, but side effects include hyperthermia and partial loss of heat sensitivity, leading to most research being halted. This project will conduct a set of preclinical proof-of-concept studies in rats to support the claims that, at doses that have minimal, clinically acceptable, or negligible impact on cardiovascular function, a2 adrenoceptor agonists can diminish thermoregulatory effects of TRPV1 receptor antagonists.

The proposed SBIR Phase II program seeks to select a first-in-class, peripherally-restricted, and long-acting somatostatin receptor 4 (LA-SSTR4) agonist clinical candidate for development as a novel non-addictive analgesic able to replace opioids for the treatment of moderate-to-severe chronic pain. The program is based on strong scientific evidence showing that activation of peripheral SSTR4 produces broad spectrum analgesic activity and pursues a unique therapeutic strategy.   Unlike opioids, SSTR4 agonists do not induce constipation, respiratory depression, dependence, addiction, or abuse. Finally, unlike SSTR2 and SSTR5, SSTR4 expression in the pituitary and pancreas is very low, supporting that selective SSTR4 agonists are unlikely to perturb peripheral endocrine functions. The preceding SBIR Phase I program has already established the feasibility of conjugating a short-acting, potent, and selective peptide SSTR4 agonist to the antibody carrier. The resulting LA-SSTR4 agonist lead series has high agonist potency and selectivity for SSTR4 and has demonstrated antinociceptive activity in an animal pain model. The proposed SBIR Phase II program seeks to: optimize the existing lead series and select a clinical candidate for development,  validate and prioritize the indication(s) for clinical development using disease-relevant mouse pain models, and characterize the pharmacokinetics and safety/toxicology profile of the clinical candidate in rat and non-human primates to help design subsequent investigational new drug (IND)-enabling studies.