Funded Projects

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Project # Project Title Research Focus Area Research Program Administering IC Institution(s) Investigator(s) Location(s) Year Awarded
1U24NS113847-01
Early Phase Pain Investigation Clinical Network: Greater New York Clinical Center Clinical Research in Pain Management Early Phase Pain Investigation Clinical Network (EPPIC-Net) NINDS NEW YORK UNIVERSITY SCHOOL OF MEDICINE DOAN, LISA (contact); LIPTON, RICHARD B New York, NY 2019
NOFO Title: HEAL Initiative: Early Phase Pain Investigation Clinical Network - Specialized Clinical Centers (U24 Clinical Trials Not Allowed)
NOFO Number: RFA-NS-19-025
Summary:

The Greater New York Clinical Center (GNYCC) aims to engage experts in pain research and pain practice to build the infrastructure required to support the objectives of the Early Phase Pain Investigation Clinical Network (EPPIC-Net). The GNYCC will provide expertise and resources to perform phase 2 clinical trials to test the efficacy of novel pain treatments, as well as phenotyping and biomarker studies that will enable customized treatments. The consortium comprises four major academic centers in New York City, one of the most diverse cities in the United States and the nation’s largest metropolitan area. We will 1) build infrastructure to rapidly access clinical trial resources and a network of investigators and clinical leaders, 2) develop a plan for swift evaluation and launch of proposed studies, and 3) optimize patient retention and monitor sites to ensure protocol adherence, data quality, and efficiency.
1UG3CA261067-01
Optimizing the Use of Ketamine to Reduce Chronic Postsurgical Pain Clinical Research in Pain Management Pain Management Effectiveness Research Network (ERN) NINDS NEW YORK UNIVERSITY SCHOOL OF MEDICINE WANG, JING (contact); DOAN, LISA New York, NY 2020
NOFO Title: HEAL Initiative: Pain Management Effectiveness Research Network: Clinical Trial Planning and Implementation Cooperative Agreement (UG3/UH3 Clinical Trial Required)
NOFO Number: RFA-NS-20-028
Summary:

Approximately 20% of patients who undergo surgery develop chronic pain, or Chronic Postsurgical Pain (CPSP). CPSP is highly associated with impaired functional recovery and persistent opioid use and dependence, and current standard postoperative multimodal analgesia is only moderately effective for its prevention. This study aims to determine whether the use of ketamine during and/or after surgery prevents Post-Mastectomy Pain Syndrome (PMPS), one of the most common CPSP conditions. Ketamine is a low-risk treatment option that is easy to implement in a wide range of clinical settings. If successful, this treatment could improve postoperative pain management in individuals undergoing mastectomy and help combat the opioid epidemic.
3U24NS114416-01S1
Administrative Supplement to Support Strategies to Increase Participant Diversity, Inclusion and Engagement in EPPIC NET Clinical Research in Pain Management Early Phase Pain Investigation Clinical Network (EPPIC-Net) NINDS DUKE UNIVERSITY LIMKAKENG, ALEXANDER TAN Durham, NC 2021
NOFO Title: HEAL Initiative: Notice of Special Interest (NOSI) regarding the Availability of Administrative Supplements to Support Strategies to Increase Participant Diversity, Inclusion and Engagement in Clinical Studies
NOFO Number: NOT-NS-21-025
Summary:

A main goal of the NIH HEAL Initiative and the Early Phase Pain Intervention Clinical Network (EPPIC-Net) is to improve non-opioid pain management. This award will leverage the resources at one of EPPIC-Net’s Specialized Clinical Centers by implementing and evaluating strategies to improve the engagement, recruitment, and retention of individuals from underserved racial/ethnic minority populations to participate in EPPIC-Net clinical trials. Since environmental, cultural, and genetic factors may account for observed differences in pain responses between racial and ethnic groups, enrollment of a diverse sample in pain research is crucial to obtain a complete understanding of the effectiveness of any proposed pain therapeutic intervention. The success of these activities will be evaluated, and a toolkit will be created to define best practices that can be by other EPPIC-Net sites and additional trials.
1K12NS130673-01
University of Michigan (UM) HEAL Initiative National K12 Clinical Pain Career Development Program (UM-HCPDP) Cross-Cutting Research Training the Next Generation of Researchers in HEAL NINDS UNIVERSITY OF MICHIGAN WILLIAMS, DAVID A (contact); CLAUW, DANIEL J; HARTE, STEVEN EDWARD Ann Arbor, MI 2022
NOFO Title: HEAL Initiative: National K12 Clinical Pain Career Development Program (K12 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-22-045
Summary:

The Interagency Pain Research Coordinating Committee has reported that early-stage investigators are leaving the clinical pain research workforce for other fields. In addition, pain clinician researchers at the senior/mentor level are also exiting the field. This project will create a national training center for early-career clinicians and scientists interested in pursuing and sustaining independent careers in clinical pain research. Research will focus on rigorous scientific methods and procedures in pain research as well as the importance of stakeholder engagement.
9R42NS120548-02A1
Development of KLS-13019 for Neuropathic Pain Cross-Cutting Research Small Business Programs NINDS KANNALIFE SCIENCES, INC. BRENNEMAN, DOUGLAS ERIC (contact); WARD, SARA J Lloyd Harbor, NY 2021
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
Summary:

Neuropathic pain adversely affects quality of life and remains challenging to treat, presenting high unmet medical need. One example of this type of pain, chemotherapy-induced peripheral neuropathy, is a chronic, severely debilitating consequence of cancer therapy for which there are no effective treatment strategies. This research is testing a new cannabidiol (CBD) analogue (KLS-13019) with neuroprotective properties and which has improved drug-like properties compared to CBD. This project will optimize the process to manufacture KLS-13019, develop analytical methods, optimize its formulation, evaluate its safety and toxicity, and test KLS-13019’s efficacy of in a rat model of chemotherapy-induced peripheral neuropathy.
5R01NS102432-02
AIBP and regulation of neuropathic pain Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NINDS Univ. of Calif., U.C. San Diego Miller, Yury La Jolla, CA 2018
NOFO Title: Administrative Supplements for Validation of Novel Non-Addictive Pain Targets (Clinical Trials Not Allowed)
NOFO Number: NOT-NS-18-073
Summary:

Persistent pain states arising from inflammatory conditions, such as in arthritis, diabetes, HIV, and chemotherapy, exhibit a common feature in the release of damage-associated molecular pattern molecules, which can activate toll-like receptor-4 (TLR4). Previous studies suggest that TLR4 is critical in mediating the transition from acute to persistent pain. TLR4 as well as other inflammatory receptors localize to lipid raft microdomains on the plasma membrane. We have found that the secreted apoA-I binding protein (AIBP) accelerates cholesterol removal, disrupts lipid rafts, prevents TLR4 dimerization, and inhibits microglia inflammatory responses. We propose that AIBP targets cholesterol removal to lipid rafts harboring activated TLR4. The aims of this proposal are to: 1) determine whether AIBP targets lipid rafts harboring activated TLR4; 2) test whether AIBP reduces glial activation and neuroinflammation in mouse models of neuropathic pain; and 3) identify the origin and function of endogenous AIBP in the spinal cord.
1R01NS117340-01
B Lymphocyte-Mediated Autoimmunity in Pain After Trauma Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NINDS PALO ALTO VETERANS INSTIT FOR RESEARCH CLARK, DAVID J Palo Alto, CA 2020
NOFO Title: Discovery and Validation of Novel Targets for Safe and Effective Pain Treatment (R01 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-18-043
Summary:

A major recent advancement for the field of pain research is the recognition of immune system dysregulation as a contributor to the most serious adverse consequences of pain from injury. Accumulating data from clinical and laboratory studies place the activation of B lymphocytes at the center of much of this work, particularly with respect to chronic pain and disability-related outcomes. Validation of this B cell hypothesis could lead directly to trials testing the efficacy of novel or existing immunomodulating agents on posttraumatic pain. To achieve these goals a well-validated core mouse model of limb fracture will be employed with additional studies to be conducted in incisional and nerve injury models to broaden the assessment of B cell mediated effects on pain. Age and sex will be included as variables to enhance rigor.
1RF1NS113883-01
Sympathetic-mediated sensory neuron cluster firing as a novel therapeutic target for neuropathic pain Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NINDS JOHNS HOPKINS UNIVERSITY DONG, XINZHONG Baltimore, MD 2019
NOFO Title: Discovery and Validation of Novel Targets for Safe and Effective Pain Treatment (R01 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-18-043
Summary:

An important component of neuropathic pain is spontaneous or ongoing pain, such as burning pain or intermittent paroxysms of sharp and shooting pain, which may result from abnormal spontaneous activity in sensory nerves. However, due to technical limitations, spontaneous activity in sensory neurons in vivo has not been well studied. Using in vivo imaging in genetically-modified mice, preliminary findings identified spontaneously-firing clusters of neurons formed within the dorsal root ganglia (DRG) after traumatic nerve injury that exhibits increased spontaneous pain behaviors. Furthermore, preliminary evidence has been collected that cluster firing may be related to abnormal sympathetic sprouting in the sensory ganglia. This project will test the hypothesis that cluster firing is triggered by abnormal sympathetic inputs to sensory neurons, and that it underpins spontaneous paroxysmal pain in neuropathic pain models. Findings from this project will identify potential novel therapeutic targets for the treatment of neuropathic pain.
1R61NS113329-01
Discovery of Biomarker Signatures Prognostic for Neuropathic Pain after Acute Spinal Cord Injury Preclinical and Translational Research in Pain Management Discovery and Validation of Biomarkers, Endpoints, and Signatures for Pain Conditions NINDS UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON HERGENROEDER, GEORGENE W Houston, TX 2019
NOFO Title: Discovery of Biomarkers, Biomarker Signatures, and Endpoints for Pain (R61/R33 Clinical Trial Optional)
NOFO Number: RFA-NS-18-041
Summary:

Debilitating neuropathic pain occurs in 40 percent to 70 percent of people who suffer from spinal cord injury (SCI). There are no distinguishing characteristics to identify who will develop neuropathic pain. The objective of this research is to develop a biomarker signature prognostic of SCI-induced neuropathic pain (NP). The aims of the project are to (1) identify autoantibodies in plasma samples from acute SCI patients to CNS autoantigens and determine the relationship between autoantibodies levels to the development of NP, (2) identify the autoantibody combination with maximal prognostic accuracy for the development of NP at six months after SCI, and (3) develop and optimize an assay to simultaneously measure several autoantibodies and independently validate the prognostic efficacy for NP using plasma samples collected prospectively. Establishing a panel will refine the prognostic value of these autoantibodies as biomarkers to detect who are vulnerable to NP and may be used to for development of nonaddictive pain therapeutics.
1R61NS113269-01
Validation of a novel cortical biomarker signature for pain Preclinical and Translational Research in Pain Management Discovery and Validation of Biomarkers, Endpoints, and Signatures for Pain Conditions NINDS University of Maryland, Baltimore SEMINOWICZ, DAVID Baltimore, MD 2019
NOFO Title: Discovery of Biomarkers, Biomarker Signatures, and Endpoints for Pain (R61/R33 Clinical Trial Optional)
NOFO Number: RFA-NS-18-041
Summary:

Chronic pain is a major health burden associated with immense economic and social costs. Predictive biomarkers that can identify individuals at risk of developing severe and persistent pain, which is associated with worse disability and greater reliance on opioids, would promote aggressive, early intervention that could halt the transition to chronic pain. The applicant’s team uncovered evidence of a unique cortical biomarker signature that predicts pain susceptibility (severity and duration). This biomarker signature could be capable of predicting the severity of pain experienced by an individual minutes to months in the future, as well as the duration of pain (time to recovery). Analytical validation of this biomarker will be conducted in healthy participants using a standardized model of the transition to sustained myofascial temporomandibular pain. Specifically the biomarker signature will be tested for its ability to predict an individual’s pain sensitivity, pain severity, and pain duration and will perform initial clinical validation.
3R01NS118563-01A1S1
Diversity Supplement to FKBP51 Antagonism to Prevent Chronic Pain: Optimizing Efficacy & Evaluating Safety and Mechanisms Cross-Cutting Research Training the Next Generation of Researchers in HEAL NINDS UNIV OF NORTH CAROLINA CHAPEL HILL LINNSTAEDT, SARAH; MCLEAN, SAMUEL A Chapel Hill, NC 2022
NOFO Title: Notice of Special Interest to Encourage Eligible NIH HEAL Initiative Awardees to Apply for PA-20-222: Research Supplements to Promote Diversity in Health-Related Research (Admin Supp - Clinical Trial Not Allowed)
NOFO Number: NOT-NS-20-107; PA-21-071
Summary:

Current evidence indicates that chronic pain after a traumatic injury is influenced by the body’s response to stress. This project will conduct a comprehensive analysis of gene expression after traumatic stress exposure in a range of animal models in various body regions including the brain (amygdala, hippocampus, hypothalamus) and spinal cord, as well as nerves and immune cells throughout the body. These studies will be conducted in animals with no stress exposure as well as in animals treated with a molecule (FKBP51) known to block the stress response. This research will enhance understanding of how FKBP51 and post-injury stress affect pain processes.
2SB1NS119103-04
Novel non-narcotic analgesic for acute and chronic pain Cross-Cutting Research Small Business Programs NINDS SOUTH RAMPART PHARMA, LLC NAISMITH, ROBERT New Orleans, LA 2023
NOFO Title: HEAL Commercialization Readiness Pilot (CRP) Program: Embedded Entrepreneurs for Small Businesses in Pain Management (SB1 Clinical Trial Not Allowed)
NOFO Number: PAR-23-069
3U24NS113850-03S1
Clinical Coordinating Center for the Health Initiative in Early Phase Pain Investigation Clinical Network - Murray Supplement Clinical Research in Pain Management Early Phase Pain Investigation Clinical Network (EPPIC-Net) NINDS MASSACHUSETTS GENERAL HOSPITAL FAVA, MAURIZIO (contact); EDWARDS, ROBERT R; RATHMELL, JAMES P Boston, MA 2021
NOFO Title: Notice of Special Interest to Encourage Eligible NIH HEAL Initiative Awardees to Apply for Administrative Supplements to Support Career Enhancement Related to Clinical Research on Pain (Admin Supp – Clinical Trial Not Allowed)
NOFO Number: NOT-NS-21-048
Summary:

Key goals of the NIH HEAL Initiative are improving non-opioid pain management and expanding the workforce of clinical researchers working on individualized pain treatments know as pain precision medicine. This award enables an exceptional early career clinician with the opportunity to obtain expertise with high-quality pain-related biomarker assessment methods and biomarker-informed clinical trial design. This research centers on eating-related gastrointestinal functional/motility pain disorders – an understudied area of clinical pain science – and will prepare the clinician to be a future leader in the clinical pain research community.
1R61NS129050-01
Integrating Nonpharmacologic Strategies for Pain with Inclusion, Respect, and Equity (INSPIRE): Tailored Digital Tools, Telehealth Coaching, and Primary Care Coordination Clinical Research in Pain Management Advancing Health Equity in Pain Management NINDS University of California, San Francisco SATTERFIELD, JASON M San Francisco, CA 2022
NOFO Title: HEAL Initiative: Advancing Health Equity in Pain Management (R61/R33 Clinical Trial Required)
NOFO Number: NS22-002
Summary:

There is a need to improve access to treatments and address the stigma, bias, and mistrust that harm and isolate people with chronic pain, especially those from ethnic and racial minority populations. The Integrating Nonpharmacologic Strategies for Pain with Inclusion, Respect, and Equity (INSPIRE) Chronic Pain (CP) intervention blends cognitive-behavioral therapy, physical therapy, mindfulness, and pain education, and is delivered by a trilingual mobile app and supported by a telehealth pain coach who coordinates with doctors. The coach will collect and summarize patient reports on pain, depression, anxiety, substance use, and social factors, and share them with healthcare providers. In this project, researchers will create the digital tool and coaching protocol, develop educational and implementation strategies for healthcare providers, and conduct a pilot test. They will then perform a randomized clinical trial to compare INSPIRE to current treatment, analyze its effects, and evaluate outcomes.
1R24NS132283-01
PURPOSE: Positively Uniting Researchers of Pain to Opine, Synthesize, and Engage Cross-Cutting Research Training the Next Generation of Researchers in HEAL NINDS NEUROVATIONS COVERSTONE, JACOB SUTTON Napa, CA 2022
NOFO Title: Emergency Awards: HEAL Initiative: Coordinating Center for National Pain Scientists Career Development (R24 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-22-060
Summary:

The Interagency Pain Research Coordinating Committee has identified a need for organized opportunities for early-stage pain researchers to meet and learn from more experienced pain researchers and mentors – who are exiting the field at a faster rate than they are being replaced. This project will create a coordinating center for early-stage pain researchers, with an online networking platform to encourage interactions and collaboration among these scientists. The research will also develop a training curriculum and make it accessible to NIH funded, early-stage pain scientists.
3R01NS102432-02S1
AIBP AND REGULATION OF NEUROPATHIC PAIN Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NINDS UNIVERSITY OF CALIFORNIA, SAN DIEGO MILLER, YURY; YAKSH, TONY L. LA JOLLA, CA 2019
NOFO Title: Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)
NOFO Number: PA-18-591
Summary:

Persistent pain states arising from inflammatory conditions, such as in arthritis, diabetes, HIV, and chemotherapy, exhibit a common feature in the release of damage-associated molecular pattern molecules, which can activate toll-like receptor-4 (TLR4). Previous studies suggest that TLR4 is critical in mediating the transition from acute to persistent pain. TLR4 as well as other inflammatory receptors localize to lipid raft microdomains on the plasma membrane. We have found that the secreted apoA-I binding protein (AIBP) accelerates cholesterol removal, disrupts lipid rafts, prevents TLR4 dimerization, and inhibits microglia inflammatory responses. We propose that AIBP targets cholesterol removal to lipid rafts harboring activated TLR4. The aims of this proposal are to: 1) determine whether AIBP targets lipid rafts harboring activated TLR4; 2) test whether AIBP reduces glial activation and neuroinflammation in mouse models of neuropathic pain; and 3) identify the origin and function of endogenous AIBP in the spinal cord.
1R01DE029951-01
Targeting Endosomal Receptors for Treatment of Chronic Pain Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NINDS COLUMBIA UNIVERSITY HEALTH SCIENCES BUNNETT, NIGEL W; SCHMIDT, BRIAN L New York, NY 2020
NOFO Title: Discovery and Validation of Novel Targets for Safe and Effective Pain Treatment (R01 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-18-043
Summary:

Many non-opioid drugs target G Protein-Coupled Receptors (GPCRs), a family of proteins involved in many pathophysiological processes including pain, fail during clinical trials for unknown reasons. A recent study found GPCRs not only function at the surface of nerve cells but also within a cell compartment called the endosome, where their sustained activity drives pain. This study will build upon this finding and test whether the clinical failure of drugs targeting plasma membrane GPCRs is related to their inability to target and engage endomsomal GPCRs (eGPCRs). This study will use stimulus-responsive nanoparticles (NP) to encapsulate non-opioid drugs and selectively target eGPCR dyads to investigate how eGCPRs generate and regulate sustained pain signals in neuronal subcellular compartments. This study will also validate eGCPRs as therapeutic targets for treatment of chronic inflammatory, neuropathic and cancer pain. Using NPs to deliver non-opioid drugs, individually or in combinations, directly into specific compartments in nerve cells could be a potential strategy for new pain therapies.
5R01NS094461-04
Clustering of individual and diverse ion channels together into complexes, and their functional coupling, mediated by A-kinase anchoring protein 79/150 in neurons Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NINDS UNIVERSITY OF TEXAS HLTH SCI CTR SAN ANTONIO SHAPIRO, MARK S San Antonio, TX 2018
NOFO Title: Administrative Supplements for Validation of Novel Non-Addictive Pain Targets (Clinical Trials Not Allowed)
NOFO Number: NOT-NS-18-073
Summary:

Multi-protein complexes have emerged as a mechanism for spatiotemporal specificity and efficiency in the function and regulation of cellular signals. Many ion channels are clustered either with the receptors that modulate them or with other ion channels whose activities are linked. Often, the clustering is mediated by scaffolding proteins, such as AKAP79/150. We will probe complexes containing AKAP79/150 and three different channels critical to nervous function: KCNQ/Kv7, TRPV1, and CaV1.2. We will use"super-resolution" STORM imaging of primary sensory neurons and heterologously expressed tissue-culture cells, in which individual complexes can be visualized at 10–20 nm resolution with visible light. We hypothesize that AKAP79/150 brings several of these channels together to enable functional coupling, which we will examine by patch-clamp electrophysiology of the neurons. Since all three of these channels bind to AKAP79/150, we hypothesize that they co-assemble into complexes in neurons and that they are dynamically regulated by other cellular signals.
1R61NS127285-01
Development of Therapeutic Antibodies to Target Sodium Channels Involved in Pain Signaling Preclinical and Translational Research in Pain Management Development and Optimization of Non-Addictive Therapies to Treat Pain NINDS University of California, Davis YAROV-YAROVOY, VLADIMIR M (contact); TRIMMER, JAMES S Davis, CA 2022
NOFO Title: HEAL Initiative: Planning Studies for Initial Analgesic Development [Small Molecules and Biologics] (R61 Clinical Trial Not Allowed)
NOFO Number: NS21-029
Summary:

Voltage-gated sodium channels such as Nav1.7, Nav1.8, and Nav1.9 transmit pain signals in nerve fibers and are molecular targets for pain therapy. While Nav channels have been validated as pharmacological targets for the treatment of pain, available therapies are limited due to incomplete efficacy and significant side effects. Taking advantage of recent advances in structural biology and computational-based protein design, this project aims to develop antibodies to attach to Nav channels and freeze them in an inactive state. These antibodies can then be further developed as novel treatments for chronic pain.
9SB1NS137964-04
Advancing precision pain medicines to the clinic Cross-Cutting Research Small Business Programs NINDS NAVEGA THERAPEUTICS, INC. MORENO, ANA MARIA (contact); ALEMAN GUILLEN, FERNANDO San Diego, CA 2023
NOFO Title: HEAL Commercialization Readiness Pilot (CRP) Program: Embedded Entrepreneurs for Small Businesses in Pain Management (SB1 Clinical Trial Not Allowed)
NOFO Number: PAR-23-069
1R41NS132625-01A1
Opioid-Sparing Non-Surgical, Bioresorbable Nerve Stimulator for Pain Relief Cross-Cutting Research Small Business Programs NINDS VANISH THERAPEUTICS INC. CUI, XINYAN TRACY Mars, PA 2023
NOFO Title: HEAL Initiative: Development of Therapies and Technologies Directed at Enhanced Pain Management (R41/R42 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-23-007
Summary:

Nerve stimulators are devices surgically implanted near a peripheral nerve or on the spinal cord that use electrical signals to reduce the perception of pain. Although these devices can provide effective pain relief to patients, many have high complication rates, resulting from the wire moving, breaking, not working, or the implantable battery pack or permanent wire causing new pain. This project will support the development and animal testing of a peripheral nerve stimulator to treat chronic pain which can be implanted without surgery. Once injected, the device will provide pain relief through electrical stimulation and then be safely degraded and resorbed by the body.
1UG3NS115637-01
Clinical Translation of Ultrasonic Ketamine Uncaging for Non-Opioid Therapy of Chronic Pain Preclinical and Translational Research in Pain Management Translating Discoveries into Effective Devices to Treat Pain NINDS STANFORD UNIVERSITY AIRAN, RAAG D (contact); WILLIAMS, NOLAN R Stanford, CA 2019
NOFO Title: HEAL Initiative: Translational Devices to Treat Pain (UG3/UH3 Clinical Trial Optional)
NOFO Number: RFA-NS-19-016
Summary:

The research team has developed ultrasonic drug uncaging for neuroscience, in which neuromodulatory agents are uncaged from ultrasound-sensitive biocompatible and biodegradable drug-loaded nanocarriers. This project will clinically translate ultrasonic ketamine uncaging for chronic pain therapy. In the UG3 phase, the research team will scale our nanoparticle production processes to human scales and adapt them to pharmaceutical standards. In the UH3 phase, they will complete a first-in-human evaluation of the safety and efficacy of ultrasonic ketamine uncaging by quantifying how much ketamine is released relative to the ultrasound dose and assessing whether the uncaged ketamine can modulate the sensitivity and affective response to pain, in patients suffering from chronic osteoarthritic pain. This project aims to yield a novel, noninvasive, non-opioid therapy for chronic pain that maximizes the therapeutic efficacy of ketamine over its side effects, by targeting its action to a critical hub of pain processing.
1U24NS115691-01
UPENN HEAL - Pain Clinical Trial Network Specialized Clinical Center Clinical Research in Pain Management Early Phase Pain Investigation Clinical Network (EPPIC-Net) NINDS UNIVERSITY OF PENNSYLVANIA FARRAR, JOHN T (contact); ASHBURN, MICHAEL ALAN Philadelphia, PA 2019
NOFO Title: HEAL Initiative: Early Phase Pain Investigation Clinical Network - Specialized Clinical Centers (U24 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-19-036
Summary:

EPPIC-Net will provide a robust and readily accessible infrastructure for the rapid implementation and performance of high-quality comprehensive studies of patients with well-defined pain conditions, and the rapid design and performance of high-quality Phase 2 clinical trials to test promising novel therapeutics for pain. Using the Hospital of the University of Pennsylvania as a hub and five additional centers that are part of the UPenn Health System and the Children’s Hospital of Philadelphia (CHOP) as spokes, studies will be conducted as designed by the expertise of the EPPIC Network, which intends to bring intense focus to relatively small numbers of patients with clinically well-defined pain conditions and high unmet therapeutic needs. The UPenn Specialized Clinical Center (SCC) will test novel, efficient study designs including adaptive and platform designs, validation studies of biomarkers, and biomarker-informed proof of principle or target engagement studies in Phase 2 trials of interventions from academic and industry partners.
3R01NS098826-02S1
PROTEASE ACTIVATED RECEPTOR TYPE 2 TARGETING FOR MIGRAINE PAIN Preclinical and Translational Research in Pain Management NINDS UNIVERSITY OF TEXAS DALLAS PRICE, THEODORE J; BOITANO, SCOTT; DUSSOR, GREGORY O; VAGNER, JOSEF RICHARDSON, TX 2018
NOFO Title: Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)
NOFO Number: PA-18-591
Summary:

Migraine is the most common neurological disorder. Currently available treatments fail to effectively manage migraine in most patients. Development of new therapeutics has been slow due in large part to a poor understanding of the underlying pathology of migraine. Endogenous proteases, released in the meninges by resident mast cells, have been proposed as a potential driver of migraine pain via an action on protease activated receptor type 2 (PAR2). The central hypothesis is that PAR2 expression in nociceptors that project to the meninges plays a key role in the pathogenesis of migraine pain. The aims are to: 1) use the established PAR2 development pipeline to design new PAR2 antagonists with improved drug-like properties; 2) use pharmacological tools in a novel mouse migraine model to further understand the potential role of PAR2 in migraine; and 3) use mouse genetics to study the cell type–specific role of PAR2 in migraine pain.
1R43NS115312-01
Long-acting ghrelin for neuropathy Cross-Cutting Research Small Business Programs NINDS EXTEND BIOSCIENCES, INC. SOLIMAN, TARIK Newton, MA 2019
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:

There is a need for safe, effective, well- tolerated drugs to treat painful neuropathy by halting or reversing the underlying pathology of the disease. One promising approach to treating painful neuropathy without opioids is the use of ghrelin, a 28-amino acid acylated peptide hormone. However, it has a short half-life and must be delivered via a constant intravenous infusion to have a therapeutic effect. Extend Biosciences' D-VITylation platform technology is truly enabling for small peptide-based therapeutics that are rapidly cleared from the bloodstream by renal filtration. The platform harnesses the naturally long half-life of vitamin D and its dedicated binding protein, VDBP. When the vitamin D molecule is conjugated to a biological therapeutic, it dramatically improves the half-life and bioavailability of the drug. Use of the technology should also allow the drug to be self-administered by subcutaneous injection. This would be of significant benefit to patients. In this project, the team will test the efficacy of EXT405 in a cell-based model of neuropathy as well as in animal models of CIPN and diabetes- induced neuropathy.