Funded Projects

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Project # Project Title Research Focus Area Research Program Administering IC Institution(s) Investigator(s) Location(s) Year Awarded
1R41NS116784-01
Discovery of T-type Calcium Channel Antagonists from Multicomponent Reactions and Their Application in Paclitaxel-induced Peripheral Neuropathy Cross-Cutting Research Small Business Programs NINDS REGULONIX, LLC KHANNA, RAJESH Tucson, AZ 2019
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.
1R01NS131165-01A1
Validation of Neuropilin-1 Receptor Signaling in Nociceptive Processing Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NINDS NEW YORK UNIVERSITY KHANNA, RAJESH New York, NY 2023
NOFO Title: HEAL Initiative: Discovery and Validation of Novel Targets for Safe and Effective Pain Treatment (R01 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-22-034
Summary:

Neuropilin 1 receptor (NRP1) is a protein receptor that is active in neurons and is hypothesized to be a key mediator of sensory neuron sensitization that can lead to pain. This project will study the cellular mechanisms by which NRP1 leads to sensitization and which cell types—sensory neurons, microglia, or both—are responsible for NRP1’s role in pain. The findings can help validate NRP1 in sensory neurons and the spinal cord as a target to treat pain following nerve injury.
2R44DA050360-02
Delivering Transcutaneous Auricular Neurostimulation as an Adjunct Treatment for Neonatal Opioid Withdrawal Syndrome Cross-Cutting Research Small Business Programs NIDA SPARK BIOMEDICAL, INC. KHODAPARAST, NAVID (contact); JENKINS, DOROTHEA DENISE Friendswood, TX 2021
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
1R43DA050360-01
Transcutaneous auricular neurostimulation for neonatal abstinence syndrome Cross-Cutting Research Small Business Programs NIDA SPARK BIOMEDICAL INC KHODAPARAST, NAVID (contact); JENKINS, DOROTHEA DENISE Friendswood, TX 2019
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:

As of 2012, an infant with neonatal abstinence syndrome (NAS) was born every 25 minutes in the United States, accounting for more than $1.5 billion in national health care expenditures. These infants frequently require hospital stay in a neonatal intensive care unit (NICU), with an average hospital stay of 25 days at an average treatment cost of $66,000. Treatment of NAS usually follows a multimodal regime based on drug therapy with an oral morphine solution, mostly in combination with a sedative, but there is a need for nonpharmacological approaches. This project will test a transcutaneous auricular neurostimulation device to help NAS babies recover from opioid withdrawal without harmful side effects. The non-invasive, auricular neurostimulation device will be placed around the ear (similar to a hearing aid), and stimulation will be delivered transcutaneously.
1R01HL150836-01
Sleep, opiate withdrawal and the N/OFQ - NOP system New Strategies to Prevent and Treat Opioid Addiction Sleep Dysfunction as a Core Feature of Opioid Use Disorder and Recovery NHLBI SRI International KILDUFF, THOMAS S (contact); BRUCHAS, MICHAEL R Menlo Par, CA 2019
NOFO Title: HEAL Initiative: Sleep and Circadian-Dependent Mechanisms Contributing to Opiate Use Disorder (OUD) and Response to Medication Assisted Treatment (MAT) (R01 - Clinical Trial Not Allowed)
NOFO Number: RFA-HL-19-028
Summary:

The widespread misuse of opioids has underscored the need to develop nonaddicting pain medications. Chronic pain is a major factor contributing to insomnia, and sleep disruption due to chronic pain causes patients to seek relief, exacerbating the drive for prescription opioids. In opioid use disorder, withdrawal from opiates induces insomnia, posing an additional challenge for successful abstinence. This study aims to determine whether treatment of opioid withdrawal-induced insomnia with nociceptin/orphanin FQ receptor (NOPR) agonists will mitigate the drive for opiate use. A major component of the arousal/withdrawal circuitries resides in the locus coeruleus (LC), which expresses MOPRs. The study will determine whether and how the NOPR system engages LC circuits to reduce arousal and insomnia-related phenotypes and assess the hypotheses that 1) the NOPR system is a component of the endogenous sleep/wake regulatory system and 2) NOPR agonists can act as therapeutic interventions to reduce opiate use.