Funded Projects

NOFO Title: PHS 2016-02 Omnibus Solicitation of the NIH for Small Business Technology Transfer Grant Applications (Parent STTR [R41/R42])
NOFO Number: PA-16-303
Summary:

The ability to de-risk lead compounds during pre-clinical development with advanced “organoid-on-a-chip” technologies shows promise. Development of microphysiological models of the peripheral nervous system is lagging. The technology described herein allows for 3D growth of high-density axonal fiber tracts, resembling peripheral nerve anatomy. The use of structural and functional analyses should mean drug-induced neural toxicity will manifest in these measurements in ways that mimic clinical neuropathology. The goals of this proposal are to establish our human model using relevant physiological measurements in tissues fabricated from human iPS cells and to validate the model system with a library of compounds, comparing against conventional cell culture models. Validating the peripheral nerve model system with drugs known to induce toxicity via a range of mechanisms will demonstrate the ability of the system to predict various classifications of neuropathy, yielding a high-content assay far more informative than traditional in vitro systems.

NOFO Title: HEAL Initiative: Behavioral Research to Improve MAT: Behavioral and Social Interventions to Improve Adherence to Medication Assisted Treatment for Opioid Use Disorders (R61/R33 Clinical Trial Optional)
NOFO Number: RFA-AT-19-006
Summary:

Medications for the treatment of opioid use disorders (MOUD) are effective at reducing opioid use, opioid overdose risk, and opioid-related deaths; however, retention and adherence to MOUD treatment, particularly buprenorphine (BUP), are discouragingly low. The objective of the current research is to adapt and extend a cognitive behavioral therapy-based short message system (SMS) intervention (TXT-CBT) to address MOUD treatment retention and adherence using the imFREE (Interactive Messaging for Freedom from Opioid Addiction) platform. imFREE builds upon the efficacious SMS-based TXT-CBT intervention, with content addressing retention and adherence to BUP, including mitigating risk factors for dropout, and features to notify social and provider support contacts in the face of treatment discontinuation and/or other indicators of relapse and overdose risk. By providing support to maximize BUP treatment adherence, coupled with skills to prevent relapse, imFREE may provide a cost-effective, easily deployable strategy for OUD treatment and prevention of overdose deaths.

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:

Some chemotherapy treatments damage nerves outside the brain and spinal cord. This condition, chemotherapy-induced peripheral neuropathy, involves tingling, burning, weakness, or numbness in hands and/or feet and affects nearly 70% of cancer patients receiving chemotherapy. Common pain medications, including opioids, can relieve pain for short intervals but are not suitable for long-term therapy. This project will develop and test a new type of treatment (reduced size cyclic analogs) for this condition. The research will evaluate the ability of this therapy to reduce inflammation and pain, as well as to repair nerve damage.

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

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:

Non-steroidal anti-inflammatory drugs (NSAIDs) are a first line pharmacologic pain therapy for chronic musculoskeletal pain, and rheumatoid arthritis (RA) and moderate to severe osteoarthritis (OA) specifically. However, insufficient pain relief by NSAID monotherapy has encouraged the use of combination therapy. Combinations of NSAIDs plus weak opioids are widely used although objective evidence for efficacy is limited and they have many adverse events.  A growing body of evidence suggests that ?2/?3 subtype-selective positive allosteric modulators (PAM) of the ?- aminobutyric acid A receptor (GABAAR) may effectively restore central pain regulatory mechanisms thus providing effective relief of chronic pain with reduced prevalence and severity of side-effects.  Based on these promising preliminary studies and considerable supporting literature data, the research team will test the hypothesis that combination dosing of TPA-023B with an NSAID will work synergistically to suppress the acute and chronic pain components of chronic musculoskeletal 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 Required)
NOFO Number: PA-18-573
Summary:

 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. 

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:

 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.

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:

Chronic pelvic pain is a debilitating condition that negatively affects the social and sexual quality of life for up to 20% of American women. Pelvic floor muscle (PFM) pain is caused by many factors, as well as by incorrect posture and excessive sensitization of the peripheral nervous system. This project will introduce a prototype of the Chronic Pelvic Pain (CPP) HomeTrainer that monitors, quantitatively and in real time, both PFM activation capacity and muscle interactions between the PFM and hip/trunk muscles and adapts the PFM training to the user’s needs in their own home. The proposed CPP HomeTrainer offers biofeedback to aid myofascial physical therapy and movement pattern training by tailoring the protocol to specifically correct interactions between the PFM and problematic hip/trunk muscles.

NOFO Title: HEAL INITIATIVE: Development of Therapies and Technologies Directed at Enhanced Pain Management (R43/R44 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-23-006
Summary:

Pelvic pain (PP) includes more than 20 different painful and debilitating conditions, such as urinary tract infections, menstrual cramps, endometriosis, overactive bladder, and interstitial cystitis, and affects millions of people. Globally, pelvic pain affects 1 in 5 women and 1 in 12 men. This project will develop an instrument to monitor and treat pain-associated temperature changes in the pelvic region to reduce chronic pelvic pain. This novel system is intended to be used at home with personalized settings.

NOFO Title: PHS 2018-02 Omnibus Solicitation of the NIH for Small Business Technology Transfer Grant Applications (Parent STTR [R41/R42] Clinical Trial Not Allowed)
NOFO Number: PA-18-575
Summary:

One of the current critical needs in addressing the opioid crisis is the development of new overdose-reversal interventions, including wearable technologies that can detect an (impending) overdose from physiological signals to signal for help, or trigger a coupled automated injection of naloxone. This project tests the approach of monitoring respiration by detecting the sounds of breathing in the trachea. This proposal aims to develop a machine learning algorithm that could process those sounds, detect the kinds of patterns of reduced breathing that occur during an opioid overdose, and design a miniature wireless sensor that could be used to detect those sounds. Such a sensor and algorithm could be a key component to a device to detect and intervene in overdoses.

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 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:

From 2009 to 2013, the utilization of the Schedule II opioids codeine, OxyContin, and fentanyl declined significantly, down about 14 percent for all three drugs. In sharp contrast, the use of tramadol, a Schedule IV controlled substance, increased by 32.5 percent. Schedule IV substances have lower potential for abuse and harm than Schedule II substances, and the fortuitous trend to tramadol has reduced the use of the relatively unsafe Schedule II opioids dramatically. However, tramadol is less effective in some individuals with a particular gene variant that makes them unable to metabolize it well. A new analgesic, omnitram, uses similar mechanisms to tramadol but is not as dependent on this gene. This SBIR Fast-Track project will conduct a Phase 1 clinical trial of Omnitram in normal human subjects. Success in this in-patient Phase 1 clinical trial will provide direct support for Omnitram’s continued clinical development toward FDA approval.