Funded Projects

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

To avoid the reliance on opioids for treatment of pain, researchers are investigating alternative approaches to disrupt the transmission of pain signals by specialized neurons in the body, such as dorsal root ganglion neurons in the spinal cord. Molecules called voltage-gated sodium channels that are located in the membranes of dorsal root ganglion neurons are essential for transmission of the pain signals. People carrying a specific variant of these channels, NaV1.7, are insensitive to pain; therefore, strategies to block this particular channel might help in the development of non-addictive pain treatment approaches. Navega Therapeutics is developing an innovative gene therapy that specifically targets NaV1.7. Using studies in human cell lines, they will identify the best designs to then test this gene therapy approach in human dorsal root ganglion neurons.

NOFO Title: HEAL INITIATIVE: Development of Therapies and Technologies Directed at Enhanced Pain Management (R43/R44 - Clinical Trial Required)
NOFO Number: RFA-NS-20-010
Summary:

Migraines and other headaches are often debilitating for patients, yet few treatment options providing sustained relief exist. All available therapies, including frequently prescribed opioids, have considerable side effects or limitations. Therefore, novel treatment approaches are needed to reduce or eliminate the need to use opiates and other systemic pharmaceuticals. Thermaquil Inc. has developed a new way of stopping migraine and other headache pain by noninvasively blocking pain signal transmission in the head, which in initial studies allowed patients to discontinue use of opioids and other addictive pain medications. Thermaquil will now be conducting a larger randomized controlled trial to demonstrate the safety and effectiveness of this novel approach. After a baseline period, patients will be randomly assigned to the active or control condition and receive a single treatment. The study will continue for 12 weeks with the active versus control arms, before all patients will be given active therapy for an additional 12 weeks.

NOFO Title: HEAL Initiative: Development of Therapies and Technologies Directed at Enhanced Pain Management (R41/R42 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-20-009

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:

Optogenetics is a method of controlling nerve or brain activity using light-sensitive cell receptors (opsins). Optogenetics has been used in brain research for decades, allowing researchers to understand the brain and its associated disorders by selectively turning on and off specific nerve cells. This project will develop and refine use of an opsin and a light-stimulation device to control nerve cells contributing to the sensation of pain. 

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

Most of the 200k Americans who undergo thoracotomy each year receive opiates to reduce postoperative pain because clinicians have few non-addictive, cost-effective choices to control the severe pain patients often experience in the first two weeks after surgery. Managing pain post-thoracotomy is critical to enable patients to take deep breaths and remove (via coughing) lung secretions that otherwise significantly increase risk of pneumonia and collapsed lung, hospital re-admission and morbidity. The most severe pain associated with thoracotomy is transmitted along the intercostal nerves, but no long-term analgesic or nerve block device exists that can provide safe and effective long-term reduction of pain. A reversible, patient-controlled, non- addictive, intercostal nerve block device would reduce suffering due to thoracotomy, broken ribs and herpes zoster. In this Phase I project, the team will develop a minimally invasive thermal nerve block device that can control nerve conduction by gently warming and cooling a short nerve segment between room temperature and warm water temperature. This novel approach is based on the discovery that warm and cool temperature mechanisms of nerve block are different and additive, enabling moderate-temperature nerve block by cycling neural tissues slightly above and below body temperature. Reversible thermal nerve blocks represent a completely new approach to managing 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:

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.

NOFO Title: PHS 2017-02 Omnibus Solicitation of the NIH for Small Business Technology Transfer Grant Applications (Parent STTR [R41/R42])
NOFO Number: PA-17-303
Summary:

Chemotherapy-induced peripheral neuropathy (CIPN) is detected in 64% of cancer patients during all phases of cancer. CIPN can result in chemotherapy dose reduction or discontinuation, and can also have long-term effects on the quality of life. Taxanes (like Paclitaxel) may cause structural damage to peripheral nerves, resulting in aberrant somatosensory processing in the peripheral and/or central nervous system. Dorsal root ganglia (DRG) sensory neurons as well as neuronal cells in the spinal cord are key sites in which chemotherapy induced neurotoxicity occurs. T-type Ca2+ channels are critical determinants of increased neuronal excitability and neurotransmission accompanying persistent neuropathic pain. Though Cav3.2 has been targeted clinically with small molecule antagonists, no drugs targeting these channels have advanced to phase II human clinical trials. This proposal aims to explore multicomponent reaction products, for the rapid identification of potent and selective T-type Ca2+ channel antagonists. The work proposed here is the first step in developing non-opioid pain treatments for CIPN. The team anticipates success against paclitaxel-induced chronic pain will translate into other chronic pain types as well, but CIPN provides focus for early stage proof-of-concept.

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:

As prescription opioid drug abuse and overdose-related deaths continue to skyrocket in the United States, the need for new and more effective non-addictive pain drugs to treat chronic pain remains critical. This research is conducting studies in animal models of a small molecule that has high potential to treat chronic pain conditions associated with neuropathy and/or inflammation. The goal of this project is to conduct dosing and other studies leading up to an animal model study of the potential drug in a toxicology study for 28 days. Results may lead to Investigative New Drug regulatory clearance to begin clinical studies to validate the potential drug’s efficacy and safety.

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

Over-the-counter medicines such as non-steroidal anti-inflammatory drugs are ineffective for treating severe chronic pain and may have serious side effects from continued use, which limits treatment options. A kinase (an enzyme whose activity targets a specific molecule) called TAK1 is involved in the chronic pain process. This research will develop a molecule previously shown to be effective in a model of inflammatory pain that also inhibits TAK1. A main goal will be to determine if this inhibitor (takinib analog HS-276) can cross the blood-brain barrier and, if successful, pursue FDA  Investigative New Drug-enabling safety studies leading to a Phase I clinical trial and a potential new chronic pain treatment.

NOFO Title: NINDS Renewal Awards of SBIR Phase II Grants (Phase IIB) for Pre-Clinical Research (R44)
NOFO Number: PAR-17-480
Summary:

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.

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.