Funded Projects

There is a compelling need to develop a front line, non-opioid-based acute pain management strategy for outpatient oral surgical procedures. LaunchPad Medical has developed Tetranite® (TN), a novel bone regenerative mineral-organic self-setting adhesive biomaterial. TN has been extensively studied in vivo in a canine jaw model and shown to be effective and well-tolerated. In this project, researchers will demonstrate that drug-loaded TN can be a novel route to providing localized and time release pain medication following wisdom tooth extraction by determining the release profile of various pain medications from TN at different concentrations. The ability to release pain therapeutics in a controlled fashion and directly at the site of injury offers improved pain control following oral surgical procedures without exposing the patient to opioids. This novel approach to pain management can be extended to more invasive orthopedic procedures such as joint replacement, spinal fusions or reconstructive trauma surgery. In Phase II the team will conduct an in vivo study to assess efficacy of medicated TN to address post-operative pain following wisdom tooth odontectomy, optimize incorporation and release of medications in TN formulations, develop cGMP manufacturing process for the compounded product, and ultimately conduct clinical trials for bone void filler using medicated TN.

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.

Opioids like morphine and hydrocodone are generally the most effective therapeutics for treatment of moderate to severe pain. However, their use is limited by serious side effects: tolerance, constipation, respiratory depression, physical dependence, and high addictive potential. Alternative pain relievers with the analgesic potency of conventional opioids, but devoid of narcotic side effects, are an immediate need. The goal of this project is to develop and commercialize an alternative to conventional opioid analgesics with reduced side effects and without the addictive properties common to mu-opioid agonists, targeting a new molecule in the central nervous system. This project will perform the necessary preliminary studies to prepare this new molecule for an investigational new drug application with the FDA.

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.

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.

 Quell Therapeutics uses the Optopatch platform for making all-optical electrophysiology measurements in neurons at a throughput sufficient for phenotypic screening. Using engineered optogenetic proteins, blue and red light can be used to stimulate and record neuronal activity, respectively. Custom microscopes enable electrophysiology recordings from 100’s of individual neurons in parallel with high sensitivity and temporal resolution, a capability currently not available with any other platform screening technology. Here, researchers combine the Optopatch platform with an in vitro model of chronic pain, where dorsal root ganglion (DRG) sensory neurons are bathed in a mixture of inflammatory mediators found in the joints of osteoarthritis patients. The neurons treated with the inflammatory mixture become hyperexcitable, mimicking the anticipated cellular pain response. Investigators calculate the functional phenotype of arthritis pain, which captures the difference in action potential shape and firing rate in response to diverse stimuli. The team will screen for small molecule compounds that reverse the pain phenotype while minimizing perturbation of neuronal behavior orthogonal to the pain phenotype, the in vitro “side effects.” The highest ranking compounds will be chemically optimized and their pharmacokinetic, drug metabolism, and in vivo efficacy will be characterized. The goal is to advance therapeutic discovery for pain, which may ultimately help relieve the US opioid crisis.

Thoracic (chest) surgeries often cause both short-term (acute) and long-term (chronic) pain and long-term opioid use. Unique genetic and clinical risk factors affect individual responses to surgical pain and pain medications. Current trial-and-error approaches to managing post-surgical pain and opioid prescribing are not ideal. This project will develop predictive software within a medical device that takes into account an individual’s genetic and clinical information to predict the likelihood of chronic pain following thoracic surgery. 

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.

Every year, more than 330,000 Americans are hospitalized for hip fractures. Rapid surgical intervention and pain treatment is critical to recover mobility and reduce other health complications. Ultrasound-guided regional anesthesia techniques are an effective alternative to opioid medication, but require specialized training for use in the emergency department. This project will develop and validate an easy-to-use ultrasound-based regional anesthesia guidance system, to ultimately improve access to non-opioid-pain treatment for hip fracture pain.

The Great Lakes Node of the NIDA-supported Drug Abuse Clinical Trials Network (CTN) represents all of the major academic medical centers in the Greater Chicago and Wisconsin areas and serves as a vital Midwestern hub for the CTN. This project supports a scientist from a group underrepresented in biomedicine to expand the work of this CTN node on research in several areas. These include mHealth, eHealth, artificial intelligence, natural language processing, and telehealth interventions; focus on youth/adolescent health and seniors/aging; health disparities; and professional education about opioid and substance treatment.

Neonatal Opioid Withdrawal Syndrome (NOWS) affects a growing number of neonates each year due to the ongoing opioid epidemic ravaging the United States. Complex neurobehavioral observation of newborns is the primary modality used. It is subjective and time-consuming by nature, requires significant expertise, and can lead to delays in treatment. The goal of this project is to develop an innovative, low-cost, non-invasive, and easy-to-use brain monitor to objectively assess the severity of withdrawal symptoms in newborns exposed to opioids and provide evidence-based decision support to care providers to improve both short- and long-term developmental outcomes. This device, referred to as NeoGUARD, is based on the continuous, automated, and real-time monitoring of brain function to detect EEG abnormalities shown to be related to NOWS and determine severity to guide pharmacological intervention. This study will focus on the initial prototyping and refinement of the hardware and software, as well as initial evaluations of its use.

The lack of timely data about drug use and overdose deaths has hindered the ability of communities and state agencies to allocate resources to regions where they are most needed. This project will develop a secure data pool that combines individual and community-level real-time data from multiple sources, including urine drug testing. These data will then be used to model the contribution of opioid, cocaine, and stimulant use to overdoses, overdose deaths, and cases of substance use disorder. This research will also use urine drug testing results and demographic/contextual data to identify populations and subpopulations at highest risk of drug use and overdose. This information will be displayed through a data platform tailored to the needs of end users (e.g., communities or agencies) and with user-friendly tools that help users make informed decisions on where resources are most urgently needed.

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.