NOT-HD-24-006: Notice of NICHD Withdrawal from Participation in PAR-24-063 " Blueprint Neurotherapeutics Network (BPN): Small Molecule Drug Discovery and Development for Disorders of the Nervous System (U44 Clinical Trial Optional)

Notice of NICHD Withdrawal from Participation in PAR-24-063 " Blueprint Neurotherapeutics Network (BPN): Small Molecule Drug Discovery and Development for Disorders of the Nervous System (U44 Clinical Trial Optional)”

Notice Number:

NOT-HD-24-006

Key Dates

Release Date:

February 23, 2024

Related Announcements

November 1, 2023 - Blueprint Neurotherapeutics Network (BPN): Small Molecule Drug Discovery and Development for Disorders of the Nervous System (U44 Clinical Trial Optional). See Notice PAR-24-063.

Issued by

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Purpose

The purpose of this Notice is to inform applicants that effective February 16, 2024, the NICHD will no longer participate in PAR-24-063 “Blueprint Neurotherapeutics Network (BPN): Small Molecule Drug Discovery and Development for Disorders of the Nervous System (U44 Clinical Trial Optional).”

The following changes have been made to PAR-24-063 as indicated below:

Currently Reads:

Part 1. Overview Information

Components of Participating Organizations

National Institute of Neurological Disorders and Stroke (NINDS)

National Eye Institute (NEI)

National Institute on Aging (NIA)

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

National Institute of Dental and Craniofacial Research (NIDCR)

National Institute on Drug Abuse (NIDA)

National Institute of Mental Health (NIMH)

National Center for Complementary and Integrative Health (NCCIH)

All applications to this funding opportunity announcement should fall within the mission of the Institutes/Centers. The following NIH Offices may co-fund applications assigned to those Institutes/Centers.

Office of Behavioral and Social Sciences Research (OBSSR)

Assistance Listing Number(s)

93.853, 93.867, 93.866, 93.279, 93.213, 93.121, 93.273, 93.865, 93.242

Modified to Read:

Part 1. Overview Information

Components of Participating Organizations

National Institute of Neurological Disorders and Stroke (NINDS)

National Eye Institute (NEI)

National Institute on Aging (NIA)

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

National Institute of Dental and Craniofacial Research (NIDCR)

National Institute on Drug Abuse (NIDA)

National Institute of Mental Health (NIMH)

National Center for Complementary and Integrative Health (NCCIH)

Office of Behavioral and Social Sciences Research (OBSSR)

Assistance Listing Number(s)

93.853, 93.867, 93.866, 93.279, 93.213, 93.121, 93.273, 93.242

Currently Reads:

Part 2. Full Text of Announcement, C. NIH Institute and Center Interests and Guidance

National Institute on Aging (NIA)

NIA is interested in studies that will provide drug development expertise and infrastructure support to researchers interested in developing novel small molecules aimed at modifying the behavioral symptoms in Alzheimer's disease (AD), delaying the onset or slowing the progression of AD, mild cognitive impairment (MCI), other dementias of aging and age-related cognitive decline. Ideally, this initiative is aimed at researchers who have promising small molecule compounds but lack the necessary outside expertise and infrastructure to advance these compounds to the clinic.

Researchers who may have the necessary drug development expertise and access to infrastructure to advance small molecules to the clinic should consider submitting an application to the Alzheimer's Drug Development Program (PAR 22-047) or its reissue. This program is also available to researchers who are interested in the preclinical development of small molecules and biologics.

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Alcohol interacts directly and indirectly with a wide spectrum of molecular targets in the brain, and alcohol-seeking behaviors and alcohol use disorders (AUD) involve multiple neurotransmitter systems, neuromodulators, hormones, signal transduction pathways, etc. These include signaling systems and signal transduction pathways of opioids, serotonin, dopamine, glutamate, ?-aminobutyric acid (GABA), endocannabinoids, neuropeptides (e.g. corticotropin releasing factor (CRF), neuropeptide Y, substance P), and protein kinases A and C. Numerous therapeutic agents targeting these and other molecular systems have been studied preclinically and in clinical trials. NIAAA is interested in research aimed to develop new pharmaceuticals to provide effective therapy for AUD. Studies involving novel targets previously un-recognized or understudied for the treatment of AUD are particularly encouraged. Specific genetic variants that may contribute to the risk for alcoholism and/or render alcohol dependent individuals responsive to specific therapeutic agent have been discovered. NIAAA is interested in supporting research to develop pharmaceuticals targeting individuals with identified genotypic and phenotypic characteristics to improve efficacy and safety.

National Eye Institute (NEI)

The National Eye Institute (NEI) interest in Blueprint Neurotherapeutics is to develop novel therapies to treat diseases and disorders of the visual system, especially blinding eye diseases such as cataracts, glaucoma, age-related macular degeneration, retinitis pigmentosa, ocular pain and other conditions. The NEI is also interested in other visual system disorders such as strabismus and amblyopia that could be treated with pharmacological interventions. Each project should have a well-defined endpoint, achievable within a five-year time frame, for developing a treatment for a specific disease or disorder of the visual system. The steps towards this goal should be clearly delineated in a series of milestones that support the development of a novel therapeutic that can then be tested in a clinical trial. If successful, a project funded under this program may lead to filing an IND-directed pharmacological and toxicological study, and Phase I clinical testing. Investigators are encouraged to contact NEI program staff to discuss potential research projects prior to application submission to determine alignment of the planned studies with priorities of the Institute.

National Institute of Dental and Craniofacial Research (NIDCR)

NIDCR is interested in neurotherapeutics development for painful disorders of the orofacial region including but not limited to temporomandibular joint disorder, trigeminal neuropathies, burning mouth syndrome, oral cancer pain and other conditions. Recent advances in genomics and phenotyping of subjects with orofacial pain conditions have expanded the scope of potential targets to treat these conditions. Receptor systems, ion channels, and pro- and anti-inflammatory molecules have been implicated in chronic pain. NIDCR is interested in supporting research that will lead to highly efficacious and specific pharmacological treatments for individuals with orofacial pain disorders.

Investigators are encouraged to contact NIDCR program staff to discuss potential research projects prior to application submission to determine alignment of the planned studies with priorities of the Institute mission and strategic plan.

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

The NICHD is interested in supporting neurotherapeutic research aimed to discover small molecules and compounds, and develop novel and improved pharmacotherapies for developmental disorders, diseases and conditions in pediatric population, including but not limited to:

Genomic neurodegenerative diseases that manifest in infancy or childhood;
Intellectual and developmental disabilities;
Traumatic injuries, including spinal cord injury, brain injury, and stroke, and the treatment of the chronic consequences of these conditions in pediatric populations;
Management of acute pain in critically ill pediatric patients.

Investigators are strongly encouraged to contact NICHD program staff to discuss their potential research projects prior to application submission to determine alignment of their planned studies with the NICHD's priorities and strategic plan.

National Institute of Mental Health (NIMH)

NIMH supports neuroscience research to discover the causes of mental illness and to develop more effective and safer treatments. The NIMH is interested in applications proposing development of therapies aimed at novel molecular and clinical targets for the treatment of mental disorders, especially treatment-resistant depression, bipolar disorder, schizophrenia, PTSD, and autism spectrum disorder. Studies aimed at the development of new ligands for targets where a probe or therapeutic already exists are generally of lower priority.

NIMH will only support projects entering the BPN at the Discovery (optimization of validated small molecule hits and promising lead compounds through medicinal chemistry) stage. NIMH will not support projects entering the BPN at the Development (IND enabling/GMP synthesis or Phase I trials) stage. Projects at the Development stage should consider applying to the NIMH SBIR/STTR Programs. Projects at the early clinical trials phase should consider the NIMH SBIR/STTR Programs, or look at the NIMH Support for Clinical Trials web page. Investigators are strongly encouraged to discuss their research plans with NIMH Scientific/Research contact prior to submission to determine alignment of the planned studies with NIMH priorities and to assess whether this or other NIMH funding opportunities are most appropriate. Investigators are also encouraged to review the following NIMH drug discovery NOFOs: Drug Discovery for Nervous System Disorders PAR-22-031 (R01) and PAR-22-032 (R21), Assay Development and Screening for Discovery of Validated Chemical Hits for Brain Disorders PAR-23-168 (R01), Discovery of in vivo Chemical Probes for Novel Brain Targets PAR-21-029 (R01), Discovery of Cell-based Chemical Probes for Novel Brain Targets PAR-21-028 (R21), National Cooperative Drug Discovery/Development Groups (NCDDG) for the Treatment of Mental Disorders or Alcohol Addiction (U01) PAR-22-143 and PAR-22-144 (U19).

Consistent with NIMH's Research Domain Criteria (RDoC) initiative, research projects directed towards ameliorating pathophysiology that is potentially more proximal to specific functional deficits (domains) than DSM diagnostic entities are encouraged. Additional information about the RDoC approach can be found at the RDoC website. The testing of functional domains not included specifically in RDoC may also be considered, if well justified. In vivo preclinical screening assays in animals should be carefully selected based on proposed brain targets and mechanisms of therapeutic action (see NOT-MH-19-053).

High-quality and reproducible studies that are reported to the scientific community in a transparent manner are an essential cornerstone of the research enterprise. Attention to principles of study design and transparency are essential to enable reviewers, the scientific community, and NIH to assess the quality of scientific findings. In support of this important goal, investigators must follow instructions to address Rigor and Reproducibility (http://grants.nih.gov/reproducibility/index.htm).

Further information on NIMH research priorities can be found in the NIMH Strategic Plan and NIMH National Advisory Mental Health Council (NAMHC) web page.

Applicants are strongly encouraged to discuss applications with NIMH staff listed in Section VII - Agency Contact(s) Scientific/Research Contacts.

National Institute of Neurological Disorders and Stroke (NINDS)

A list of diseases that is relevant to the research mission of the NINDS can be found at https://www.ninds.nih.gov/Disorders/All-Disorders ; applicants are encouraged to contact the NINDS to discuss disease areas of interest.

This NOFO serves as the primary support mechanism at NINDS for the discovery and development of small molecule drugs. This includes all medicinal chemistry optimization efforts requiring analog synthesis. Researchers focused on the development of biologics and biotechnology products should consider the BPN-Bio program (https://neuroscienceblueprint.nih.gov/neurotherapeutics/bpn-biologics ). Applicants seeking support only to conduct early stage clinical trials should consider applying for an NINDS Exploratory Clinical Trials R01, through PAR-21-233, which provides additional flexibility in budget and time, as well as the option of including a phase II trial.

There is growing recognition that the quality and reproducibility of both preclinical and clinical research depend on the rigor with which researchers conduct studies, control for potential bias, and report essential methodological details. Examples of critical elements of a well-designed study are summarized on the NINDS website http://www.ninds.nih.gov/funding/transparency_in_reporting_guidance.pdf. NINDS urges applicants to this program to consider these elements when describing supporting data and proposed studies.

National Center for Complementary and Integrative Health (NCCIH)

NCCIH supports neurotherapeutic research to discover and develop small molecules that fall within the definition of a secondary metabolite (i.e., natural products) inclusive of the array of chemical space derived from botanicals, microorganisms (e.g., commensal microbes), marine invertebrates, and venomous species. The NCCIH is interested in applications proposing development of interventions to modulate CNS-based symptoms with priority given to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), pain and pain related symptoms including sleep, stress, and mood disorders. Investigators are strongly encouraged to discuss their research plans with the NCCIH Scientific/Research contact prior to submitting their applications.

National Institute on Drug Abuse (NIDA)

Through participating in this NOFO, NIDA aims to provide drug development expertise and access to resources to support the drug addiction researchers interested in developing new molecular entities for the treatment of substance use disorders (SUD).

NIDA will only support the projects entering the BPN at the Discovery stage. Specifically, NIDA is interested in using the BPN mechanism to support projects in the "hit to lead optimization" stages with a well-justified proposal for the development stage as well.

NIDA applicants are strongly encouraged to take full advantage of the opportunities the BPN affords, including collaboration with BPN consultants and NIH-supported contract research organizations (CROs) that specialize in medicinal chemistry, pharmacokinetics, toxicology, formulations development, chemical synthesis under Good Manufacturing Practices (GMP). Researchers, who already possess the drug development expertise and access to the necessary R&D infrastructure in their home institutions, should consider submitting their applications to the specialized NIDA programs administered by the NIDA Division of Therapeutics and Medical Consequences (DTMC).
Investigators are strongly encouraged to discuss their research plans with NIDA program staff prior to submission to determine alignment of the planned studies with NIDA's interest and priorities. NIDA staff will also provide help in assessing whether this or other NIDA funding opportunities would be the most appropriate.

Modified to Read:

Part 2. Full Text of Announcement, C. NIH Institute and Center Interests and Guidance

National Institute on Aging (NIA)

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

National Eye Institute (NEI)

National Institute of Dental and Craniofacial Research (NIDCR)

National Institute of Mental Health (NIMH)

Further information on NIMH research priorities can be found in the NIMH Strategic Plan and NIMH National Advisory Mental Health Council (NAMHC) web page.

Applicants are strongly encouraged to discuss applications with NIMH staff listed in Section VII - Agency Contact(s) Scientific/Research Contacts.

National Institute of Neurological Disorders and Stroke (NINDS)

National Center for Complementary and Integrative Health (NCCIH)

National Institute on Drug Abuse (NIDA)

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Scientific/Research Contact(s)

Charles Cywin, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1779
Email: charles.cywin@nih.gov

Jerome R. Wujek, PhD
National Eye Institute (NEI)
Telephone: 301-451-2020
Email: wujekjer@mail.nih.gov

Enrique Michelotti, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-443-5415
Email: michelottiel@mail.nih.gov

Qi-Ying Liu, MD, MSci
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-2678
Email: liuqiy@mail.nih.gov

Zhaoxia Ren, PhD
National Institute of Child Health and Human Development (NICHD)
Telephone: 301-402-9340
Email: zren@mail.nih.gov

Elena Koustova, PhD, MBA
National Institute on Drug Abuse (NIDA)
Telephone: 301-496-8768
Email: koustovae@mail.nih.gov

Yisong Wang, PhD
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-480-9483
Email:yisong.wang@nih.gov

Yolanda F. Vallejo-Estrada, Ph.D.
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-827-4655
Email: Yolanda.Vallejo-Estrada@nih.gov

Lorenzo M. Refolo, PhD
National Institute on Aging (NIA)
Telephone: (301) 594-7576
Email: refolol@mail.nih.gov

Emrin Horgusluoglu, Ph.D.
National Center for Complementary & Integrative Health (NCCIH)
Phone: 240-383-5302
Email: emrin.horgusluoglu-moloch@nih.gov

Qiying Liu
NIAAA - NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
Phone: 301-443-2678
E-mail: liuqiy@mail.nih.gov

Melissa Ghim, PhD
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-529-6570
Email: melissa.ghim@nih.gov

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