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Related Announcements

PAR-18-762 -  Innovation Grants to Nurture Initial Translational Efforts (IGNITE): Assay Development and Neurotherapeutic Agent Identification (R61/R33 Clinical Trial Not Allowed)

Issued by

National Center for Complementary and Integrative Health (NCCIH)

Purpose

The purpose of this Notice of Special Interest (NOSI) is to announce NCCIH participation in the NINDS IGNITE program. For this NOSI, NCCIH is interested in supporting research geared toward development of robust, validated analgesic assays suitable for medium- to high-throughput screening of natural product libraries. For the purposes of this NOSI, natural products are defined as extracts, chromatographic fractions, or isolated constituents derived from herbal, botanical, marine, microbial, or animal sources. For this NOSI, NCCIH is prioritizing analgesic targets relevant to musculoskeletal, neuropathic, and inflammatory pain conditions.

Background

In light of the ongoing national opioid public health crisis, discovery of new nonaddictive pain treatments is of the highest importance. Nature has been a prolific source of analgesic compounds. Much of what we know about nociception is due to discovery of natural products that illuminated the various signaling pathways and targets responsible for sensory perception of painful stimuli. Yet, despite this history, there is very limited current research devoted to discovering new natural products with analgesic activity. Thus, a renewed focus on studying natural products for pain management seems not only timely but also perhaps the most productive approach to take in our quest for solutions to the current opioid crisis.

Objectives

• • Development and validation of assay(s) (including phenotypic assays) to support discovery and prioritization of natural products with promising analgesic activity.
  • Development of in vitro or ex vivo potency/efficacy assays designed to indicate the specific ability of a natural product to achieve a desired analgesic effect.
  • Development of assays to evaluate cellular uptake, target engagement, downstream functional measures in vitro or ex vivo, or purity and specificity of analgesic natural product leads.
  • Development of assays to measure DNA, RNA, and protein levels of endogenous genes, or downstream in vitro or ex vivo functional readouts for analgesic natural products.
  • Development and optimization of analgesic assays for high-throughput screening (HTS) of natural products.
  • A combination of assays may be developed to demonstrate relevant biological activity when a single assay may not provide adequate measurement of overall potency due to a complex mechanism of action or multiple activities of a preliminary therapeutic agent.

  Examples of activities for the R33 phase include, but are not limited to:

  • Screening of natural product libraries for activity against analgesic targets via the use of automation, miniaturized assays, and large-scale data analysis.
  • Preparation and screening in analgesic assays of select subsets of natural products using, for example, chromatographic fractionation.
  • Isolation and structure elucidation of active analgesic natural products.
  • Assessment of initial pharmacokinetic parameters such as absorption, distribution, metabolism, and excretion (ADME) of promising analgesic natural products.
  • Assessment of potential off-target activities (e.g., abuse liability, respiratory depression) of promising analgesic natural products.

Applications to this NOSI must address all requirements of PAR-18-762 and will be reviewed in an appropriate Scientific Review Group organized by NINDS. If natural product screening activities are included, the library to be screened can be a publicly available or private library but must be limited to natural products only. The library may include crude extracts, chromatographic fractions, isolated compounds, or combinations of these. One notable publicly available natural products library is managed by the National Cancer Institute (https://dtp.cancer.gov/organization/npb/introduction.htm). Furthermore, medicinal chemistry efforts of any identified analgesic compounds must be limited to efforts designed explicitly to elucidate the mechanism of action of the compound (e.g., target pull down, click chemistry). Medicinal chemistry efforts for improved potency or selectivity will not be supported through this NOSI.

Application and Submission Information

This notice applies to due dates on or after October 20, 2020 and subsequent receipt dates through May 8, 2021

Submit applications for this initiative using one of the following funding opportunity announcements (FOAs) or any reissues of these announcement through the expiration date of this notice

• PAR-18-762 - Innovation Grants to Nurture Initial Translational Efforts (IGNITE): Assay Development and Neurotherapeutic Agent Identification (R61/R33 Clinical Trial Not Allowed

All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:

• For funding consideration, applicants must include “NOT-AT-20-016” (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

Although NCCIH is not listed as a Participating Organization in all the FOAs listed above, applications for this initiative will be accepted.

Applications nonresponsive to terms of this NOSI will be withdrawn from consideration for this initiative.

Inquiries

Scientific/Research Contact(s)

D. Craig Hopp, Ph.D.

National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-496-5825
Email: hoppdc@nih.gov

Peer Review Contact(s)

Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9223
Email:nindsreview.nih.gov@mail.nih.gov

Financial/Grants Management Contact(s)

Shelley Carow
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-594-3788
Email: carows@nih.gov