Drug Development/Novel Targets: Novel therapeutic agents

Initiate drug discovery efforts to develop novel therapeutic agents against at least 6 novel therapeutic targets (a minimum of three targets for presymptomatic and early stage disease and a minimum of three for advanced disease).

2026 RFA-AG-19-010: Alzheimer Centers for Discovery of New Medicines (U54 Clinical Trial Not Allowed) PAR-13-048: Drug Discovery for Nervous System Disorders (R01) PAR-16-041: Drug Discovery for Nervous System Disorders (R01) PAR-19-147: Drug Discovery for Nervous System Disorders (R01 Clinical Trials Not Allowed) PAR-13-049: Drug Discovery for Nervous System Disorders (R21) PAR-16-042: Drug Discovery for Nervous System Disorders (R21) PAR-19-146: Drug Discovery for Nervous System Disorders (R21 Clinical Trials Not Allowed) PAR-12-015: Alzheimer's Drug-Development Program (U01) PAR-15-174: Alzheimer's Drug-Development Program (U01) PAR-18-820: Alzheimer's Drug-Development Program (U01 Clinical Trial Optional) RFA-AG-13-014: Alzheimer's Disease Therapeutics Program (U01) RFA-NS-13-003: NIH Blueprint for Neuroscience Research Grand Challenge: Discovering Novel Drugs for Disorders of the Nervous System (U01) PAR-14-293: Blueprint Neurotherapeutics Network (BPN): Small Molecule Drug Discovery and Development for Disorders of the Nervous System (UH2/UH3) PAR-17-205: Blueprint Neurotherapeutics Network (BPN): Small Molecule Drug Discovery and Development for Disorders of the Nervous System (UG3/UH3) PAR-18-546: Blueprint Neurotherapeutics Network (BPN): Small Molecule Drug Discovery and Development for Disorders of the Nervous System (UG3/UH3 Clinical Trial Optional) PA-16-091: Small Business Alzheimer's Disease Research (R43/R44) PA-16-092: Small Business Alzheimer's Disease Research (R41/R42) PAS-17-064: Advancing Research on Alzheimer's Disease (AD) and Alzheimer's-Disease-Related Dementias (ADRD) (R43/R44) PAS-18-187: Advancing Research on Alzheimer's Disease (AD) and Alzheimer's-Disease-Related Dementias (ADRD) (R43/R44 Clinical Trial Optional) PAS-19-316: Advancing Research on Alzheimer's Disease (AD) and Alzheimer's-Disease-Related Dementias (ADRD) (R43/R44 Clinical Trial Optional) PAS-17-065: Advancing Research on Alzheimer's Disease (AD) and Alzheimer's-Disease-Related Dementias (ADRD) (R41/R42) PAS-18-188: Advancing Research on Alzheimer's Disease (AD) and Alzheimer's-Disease-Related Dementias (ADRD) (R41/R42 Clinical Trial Optional) PAS-19-317: Advancing Research on Alzheimer's Disease (AD) and Alzheimer's-Disease-Related Dementias (ADRD) (R41/R42 Clinical Trial Optional) PAR-19-147: Drug Discovery For Nervous System Disorders (R01 Clinical Trials Not Allowed) PAR-22-031:Drug Discovery For Nervous System Disorders (R01 Clinical Trials Not Allowed) PAR-22-032: Drug Discovery For Nervous System Disorders (R21 Clinical Trials Not Allowed) PAR-22-047: Alzheimer's Drug-Development Program (U01 Clinical Trial Optional) PAS-22-196: Advancing Research on Alzheimer's Disease (AD) and AD-Related Dementias (ADRD) (R43/R44 Clinical Trial Optional) (Reissue of PAS-19-316) PAS-22-197: Advancing Research on Alzheimer's Disease (AD) and AD-Related Dementias (ADRD) (R41/R42 Clinical Trial Optional) (Reissue of PAS-19-317) PAR-23-219: SBIR/STTR Commercialization Readiness Pilot (CRP) Program Technical Assistance and Late Stage Development (SB1, Clinical Trial Not Allowed) (Reissue of PAR-20-129) PAR-23-220: SBIR/STTR Commercialization Readiness Pilot (CRP) Program Technical Assistance and Late Stage Development (SB1 Clinical Trial Required) (Reissue of PAR-20-130) PAR-24-063: Blueprint Neurotherapeutics Network (BPN): Small Molecule Drug Discovery and Development for Disorders of the Nervous System (U44 Clinical Trial Optional) PAR-24-293: Blueprint Neurotherapeutics Network (BPN): Biologic-based Drug Discovery and Development for Disorders of the Nervous System (UG3/UH3 Clinical Trial Optional) PAR-24-294: Blueprint Neurotherapeutics Network (BPN): Biologic-based Drug Discovery and Development for Disorders of the Nervous System (U44 Clinical Trial Optional) PAR-25-051: Blueprint Neurotherapeutics Network (BPN): Small Molecule Drug Discovery and Development of Disorders of the Nervous System (UG3/UH3 Clinical Trial Optional) PAR-25-297: Alzheimer's Drug-Development Program (U01 Clinical Trial Optional) RFA-AG-25-024: Access and Manipulation of Brain Cell Subtypes Implicated in Aging and AD/ADRD (R61/R33 Clinical Trial Not allowed) RFA-AG-24-049: Artificial Intelligence in Pre-clinical Drug Development for AD/ADRD (R01 Clinical Trial Not Allowed) 6.D Achieved Initiate drug discovery efforts to develop novel therapeutic agents against at least 6 novel therapeutic targets... DN 2012 AD Summit: 1A, 1B, 1D, and 5A 2018 AD Summit: 4E 2021 AD Summit: 4.D and 4.E News: NIH-funded translational research centers to speed, diversify Alzheimer's drug discovery Highlight: Study of green tea and other molecules uncovers new therapeutic strategy for Alzheimer’s Workshop: Blood-Brain Barrier Transport in Aging and Alzheimer’s Disease Dementia with Lewy Bodies: Filling the Gaps in Translational and Clinical Research Drug Development - Novel Targets TREAT-AD Centers (U54 Clinical Trial Not Allowed) Drug Discovery for Nervous System Disorders (R01) Alzheimer's Drug-Development Program (U01) Blueprint Neurotherapeutics Network (BPN): Small Molecule Drug Discovery and Development for Disorders of the Nervous System (UH2/UH3) Blueprint Neurotherapeutics Program: BPN Success Stories NIA-AA Symposium: Enabling Precision Medicine for Alzheimer's Disease Through Open Science Select projects funded in FY21 Pharmacological Targeting of Tau Aggregates for Autophagic Removal Reshaping ApoE4 and Alzheimer's Brains with ApoE2 Nonlipogenic ABCA1 inducers for ADRD Novel Reengineered Microbiome-based Biologic Therapy to Treat Cognitive and Behavioral Symptoms of Alzheimer's Disease and Related Dementias Indiana University School of Medicine (IUSM)-Purdue TREAT-AD center 2017

  • Complete preclinical development, through IND filing, of at least 12 therapeutics agents against at least 3 novel targets (at least one novel target should be for presymptomatic disease).
  • Invest in the expansion of therapeutic modalities including natural products, gene therapy, antisense oligonucleotides, cell therapy, etc.

Summary of Key Accomplishments

NIA continues to expand the AD/ADRD therapeutic pipeline by supporting the discovery and development of new drug candidates for the treatment and prevention of AD/ADRD through multiple targeted funding initiatives. These initiatives include the AD Drug Development Program, the Small Business Program and the Blueprint Neurotherapeutics Program.

Over the past decade, 25 new drug candidates developed with NIA's support have reached Investigational New Drug (IND) status and have transitioned to clinical development.

These drug candidates are targeting a wide range of disease processes such as: neuroinflammation, lipid dysregulation, metabolic and vascular factors, protein homeostasis, synaptic plasticity, neurogenesis and multiple aspects of amyloid and tau biology. 16 of these drug candidates are in or are anticipated to start Phase I clinical trials, 8 have advanced to Phase II testing and 1 has advanced to Phase III trial. NIA has supported the clinical development of 22 of these 25 new drug candidates. It is of note that 17 of these new drug candidates are small molecules (i.e. orally bioavailable drugs that can be taken as a pill); the remaining 8 are biologics spanning multiple modalities from gene therapy and peptide drugs to various types of immunotherapy.

Among the new drug candidates ready to enter Phase I trials are:

  • DUVAX, a dual anti-amyloid/anti-tau vaccine as a disease modifying therapeutic
  • PNA5, a peptide inhibitor of the Mas receptor as a disease modifying therapeutic
  • PRX-P4-003, a selectively bioavailable dopamine and norepinephrine reuptake inhibitor for the treatment of apathy, a major neuropsychiatric symptom of AD/ADRD

Thirty-eight additional drug candidates are in various stages of preclinical drug development. These include:

  • Protein vaccine targeting alpha synuclein
  • Small molecule microtubule stabilizer aiming to decrease tau pathology
  • Small molecule inhibitor of the prostaglandin E2 receptor that decreases neuroinflammation
  • Small molecule inhibitor of INPPD that leads to increased immune receptor signaling and neuroprotection/resilience

The key accomplishments summary is current as of September 2025.