Funded Projects

We discovered a class of non-opioid modulators of the T-type Cav3.2 channel that could treat neuropathic pain. In vivo pharmacokinetic and pharmacodynamic studies and preliminary toxicological studies identified AFA-279 and other candidates, which did not produce observable side-effects and showed greater analgesic effects than other neuropathic pain medications in rodent models. The goal of this proposed project is to submit the IND application on our Cav3.2 modulator to the Food and Drug Administration (FDA). We will produce AFA-279 under Good Manufacturing Practice (GMP)–like conditions using chemical manufacturing controls for Good Laboratory Practice (GLP) nonclinical toxicity studies and GMP clinical batch future Phase 1 clinical trials, complete toxicological and safety studies to establish the safety profile of AFA-279, prepare and submit the IND application, and then initiate early clinical trials. Our ultimate goal is to deliver a safer, more effective, non-opioid Cav3.2 channel modulator to patients suffering from neuropathic pain.

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.

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.

Pain is one of the most common and debilitating symptoms of a wide range of injuries and diseases. Safe and effective alternatives for treating pain that reduce dependence on opioids are, therefore, a primary goal of the NIH. This project proposes a non-invasive, non-pharmacological alternative to treat pain by combining an innovative electroencephalography (EEG)-based Neurofeedback (NF) solution in an immersive virtual reality (VR) environment. NF and VR have been shown to independently produce ameliorative effects on pain, and it is hypothesized that an NF training in VR would have synergistic effects, as VR would distract from pain perception to improve patient compliance in more engaging NF protocols that improve their ability to control pain perception. In the scope of this project, we will initially focus our work on chronic low back pain (cLBP), as this is a growing segment of chronic pain sufferers with a 39 percent worldwide lifetime prevalence, and whose sufferers have historically been heavy users of opiates; later stages of this project will expand this application to address other forms of pain.

Chronic pain affects over 100 million Americans, costing society about $600 billion annually. Despite numerous pharmacological and non-pharmacological therapies, over 50% of chronic pain sufferers feel little control over their pain. CognifiSense has developed a patent-pending Virtual Reality Psychological Therapy (VRPT), which is designed to create lasting reduction of chronic pain by addressing the maladaptive learning processes driving pain chronification. VRPT is an experiential learning system, which provides the brain a new set of signals that teaches it that the pain is not as bad as it perceived and that it has greater control over the pain than it perceived. VRPT combines the immersive power and the ability to individualize the therapy of Virtual Reality with well-researched principles of self-distancing, self-efficacy, and extinction to retrain the brain. The goal of this study is to determine the clinical feasibility of VRPT in achieving a lasting reduction of chronic pain, establish brain mechanisms associated with treatment response, and collect comprehensive user feedback to enable further refinement of the current product prototype. CognifiSense's VRPT has the potential to be a significant clinical and business opportunity in the treatment of chronic pain.

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.

New approaches that can effectively ameliorate acute and chronic migraine pain are urgently needed. Due to its critical roles in inducing migraine pain, CGRP and its receptor complex, the calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1) have been targeted for migraine treatment. A new strategy for targeting the CGRP-mediated signaling pathway is needed to meet the medical need of migraine patients. The team developed a group of long-acting CGRP/RAMP1-specific peptide super-antagonists that form gels in situ in aqueous solution. Based on this exciting finding, the investigators propose to develop and identify the most potent antagonistic analog candidates (Aim 1), and characterize the pharmacokinetics of gel depots made of the selected candidates in vivo (Aim 2). This feasibility study is needed to explore the translational potential of these newly invented super-antagonists for the treatment of chronic migraine in combination with conventional migraine agents. 

Current agonist treatments for opioid use disorder (OUD) are not adequate to address the opioid crisis and have abuse liability concerns. Chemokines (hormones of the immune system that mediate innate immune inflammation) enhance pain, reduce opioid analgesia, and promote drug-seeking behavior and addiction—giving them a central role at the crossroads of chronic pain and the opioid crisis. So blocking chemokines (rather than opioid receptors) provides an exciting and untested treatment opportunity for pain and OUD. This proposal will assess, in animal self-administration models that mimic human drug-taking, whether a chemokine antagonist peptide R103 reduces morphine intake, as well as if R103 will prevent or blunt naloxone-precipitated withdrawal signs in morphine-dependent rats and stop relapse.