Funded Projects

NOFO Title: Developing Regulated Therapeutic and Diagnostic Solutions for Patients Affected by Opioid and/or Stimulants use Disorders (OUD/StUD) (R43/R44 - Clinical Trial Optional)
NOFO Number: RFA-DA-23-021
Summary:

Although medications for opioid use disorder are effective and available, providers currently lack methods to monitor patients and thus inform improved dosing. This project will develop Strength Band Platform, an innovative artificial intelligence-based digital platform. The wearable device will collect patient physiological characteristics to detect relapse and withdrawal during treatment with medications for opioid use disorder in real-world settings. 

NOFO Title: HEAL Initiative: America’s Startups and Small Businesses Build Technologies to Stop the Opioid Crisis (R43/R44 - Clinical Trial Optional)
NOFO Number: RFA-DA-19-019
Summary:

With the entwined crises of opioid use and chronic pain, there is a need for alternative, safe therapies to manage opioid use disorder, opioid withdrawal symptoms, chronic pain, and/or associated anxiety and depression. A proof-of-concept preclinical study has already been conducted of a cannabinoid-opioid combination that demonstrated opioid-sparing and synergistic analgesic effects, with the combination providing greater analgesia in a rodent model of chronic pain than a standard dose of the opioid alone. This proposal aims to develop a fixed-dose combination (FDC) of the cannabinoid-opioid that may have improved analgesia with lower opioid doses and thereby lower the risk of dependence, withdrawal, diversion, abuse, and overdose. Preclinical pharmacokinetic and ?in vivo ?safety studies will help determine if co-administration alters the pharmacokinetics and/or respiratory depression related to either compound in rodents.

NOFO Title: HEAL Initiative: America’s Startups and Small Businesses Build Technologies to Stop the Opioid Crisis (R43/R44 - Clinical Trial Optional)
NOFO Number: RFA-DA-19-019
Summary:

The increase in prevalence of cancer coupled with an increase in the cancer survival rates due to chemotherapy regimens is transforming cancer pain into a large, unmet medical problem. Chemotherapy-induced peripheral neuropathy (CIPN) is a common and potentially dose-limiting side effect of many cancer drug treatment regimens and is caused in part by alterations in ion channels; blocking or depleting Cav3.2 channels in dorsal root ganglion (DRG) neurons should thus mediate analgesic effects. This proposal aims to develop and test potent, orally available, and selective Cav3.2 channel antagonists, building on the structure of a medicinal plant product—betulinic acid (BA)—that has been identified to be Cav3.2-selective and antinociceptive in CIPN. Such compounds could reduce the reliance on opioids in cancer patients.

NOFO Title: HEAL Initiative: America’s Startups and Small Businesses Build Technologies to Stop the Opioid Crisis (R43/R44 - Clinical Trial Optional)
NOFO Number: RFA-DA-19-019
Summary:

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.

NOFO Title: HEAL Initiative: Development of Therapies and Technologies Directed at Enhanced Pain Management (R43/R44 – Clinical Trial Not Allowed)
NOFO Number: RFA-NS-20-011
Summary:

Spinal cord stimulation (SCS) has been shown to provide effective relief for most people with chronic pain and eliminated the need for opioid therapy in more than half of those treated. However, traditional SCS approaches have encountered problems when glial cells coat the stimulation electrodes that distance the device from targeted neurons. This project will develop a novel hybrid Closed Loop Omnidirectional Neuromodulation with Electromagnetic fields (CLONE) system that is combined with magnetic-based stimulation to overcome glial coating of SCS electrodes, better target neurons in dorsal spine tissue, which may lead to better treatment of chronic neuropathic neck and low back pain.

NOFO Title: PHS 2017-02 Omnibus Solicitation of the NIH, CDC, and FDA for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44])
NOFO Number: PA-17-302
Summary:

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.

NOFO Title: Development of a Device to Objectively Measure Pain (R43/R44)
NOFO Number: RFA-DA-18-012
Summary:

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.

NOFO Title: HEAL Initiative: America’s Startups and Small Businesses Build Technologies to Stop the Opioid Crisis (R43/R44 - Clinical Trial Optional)
NOFO Number: RFA-DA-19-019
Summary:

Opioid agonist therapy (OAT), such as buprenorphine/naloxone (BUP/NAL), is proven effective against opioid use disorder (OUD), but poor medication adherence is a major barrier. This project aims to substantially increase adherence to oral BUP/NAL with Pillsy, a smart technology platform, which acts like a digital medication coach, providing education and reminders using a mobile app, text messages, and automated phone calls. The platform is built around a Bluetooth-based smart pill bottle cap that automatically tracks doses and timing, and sends intelligent reminders to create a unique feedback loop, which allows constant optimization of the incentive/reminder messages to meet user needs to increase adherence. A dashboard enables providers to easily track medication use and patient engagement. The Pillsy platform only nominally increases the cost of oral BUP/NAL treatment, and physicians can bill for monitoring time (CPT code 99091). The project team will adapt the current Pillsy platform and perform a randomized efficacy trial of BUP/NAL adherence.

NOFO Title: HEAL Initiative: Development of Therapies and Technologies Directed at Enhanced Pain Management (R43/R44 - Clinical Trial Not Allowed)
NOFO Number: RFA-NS-20-011
Summary:

Pelvic venous compression is a common cause of chronic pelvic pain in women. Because many women do not receive an accurate diagnosis for the cause of their pelvic pain, some take opioids to help manage their symptoms. This project will further develop a new diagnostic system specifically designed to treat limited blood flow in pelvic region. This system visualizes pelvic veins toward development of a method to relieve pressure that causes pain. 

NOFO Title: PHS 2018-02 Omnibus Solicitation of the NIH, CDC, and FDA for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Not Allowed)
NOFO Number: PA-18-574
Summary:

Chronic focal neuropathic pain, which includes pain etiologies such as radiculopathy and radiculitis, focal peripheral neuropathies, and low back pain, affects as many as 25 million patients annually in the United States. Chronic focal neuropathic pain is maintained by genome-wide transcription regulation in the dorsal root ganglia (DRG) / spinal cord network. The transcription factors driving this regulation constitute a promising class of targets with the potential to alter the course of pain with a single treatment. DNA decoys are oligonucleotides that specifically inhibit the activity of certain transcription factors. AYX2 binds and inhibits Krüppel-like transcription factors (KLF) in the DRG-spinal cord. The goal of this Phase 1 proposal is to advance AYX2 toward an IND submission, allowing for human clinical trials. We propose in Aim 1 to characterize AYX2 pharmacokinetics in the cerebrospinal fluid and plasma and its distribution in the DRG, spinal cord and brain following an IT injection. With this information, AYX2 will be tested in a panel of complementary toxicology studies in Aim 2 to allow for final IND-enabling studies, supported by Phase 2 of the grant. This research will accelerate development of AYX2 as a novel drug candidate for the non-opioid treatment of pain.

NOFO Title: Developing Regulated Therapeutic and Diagnostic Solutions for Patients Affected by Opioid and/or Stimulants use Disorders (OUD/StUD) (R43/R44 - Clinical Trial Optional)
NOFO Number: RFA-DA-23-021
Summary:

Hospitalized patients often receive opioids for pain and sleep management, which can contribute to opioid dependence and continued use after leaving the hospital. Even when hospital stays are extended to wean people from opioids, these patients remain at increased risk for opioid use disorder and withdrawal.  This project will develop a novel small molecule medication that blocks nerve inflammation to prevent opioid dependence in hospitalized patients receiving opioids. 

NOFO Title: PHS 2018-02 Omnibus Solicitation of the NIH, CDC, and FDA for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Not Allowed)
NOFO Number: PA-18-574
Summary:

Voltage-gated sodium channels are responsible for the transmission of pain signals. Nine genes have been identified, each having unique properties and tissue distribution patterns. Genetic studies have correlated a hereditary loss-of-function mutation in one human Na+ channel isoform – ?Na?V?1.7 – with a rare genetic disorder known as Congenital Insensitivity to Pain (CIP). Individuals with CIP are not able to feel pain without any significant secondary alteration. Thus, selective inhibition of ?Na?V?1.7 in normal humans could recapitulate the phenotype of CIP. This research team developed a non-permanent gene therapy to target pain that is non-addictive (because it targets a non-opioid pathway), highly specific (only targeting the gene of interest), and long-term lasting (around 3 weeks in preliminary assays in mice). During this Phase I , the team will 1) test additional pain targets ?in vitro?, and 2) evaluate the new targets ?in vivo ?in mice models of inflammatory and neuropathic pain.