# IND Enabling Studies for a Novel Mas Receptor Agonist for Treatment of Cognitive Impairment in Patients at Risk for Alzheimer's Disease Related Dementia

> **NIH NIH U01** · UNIVERSITY OF ARIZONA · 2021 · $16,031

## Abstract

PROJECT SUMMARY
In the proposed early stage NIA U01 ADDP program, we will: 1) finalize dose-optimization of our lead compound,
2) complete PK/PD testing and, 3) begin manufacturing, formulation and the toxicological and safety analyses
required to advance our lead compound to IND submission and clinical studies for patients at risk for Vascular
Contributions to Cognitive Impairment and Dementia (VCID) and conversion to Alzheimer's Disease and Related
Dementias (ADRD). Our vision is to be a first-in-class therapy to reduce inflammatory-disease related
cognitive impairment and inhibit dementia development in patients at risk for VCID and ADRD. We will
leverage our experience with our currently approved FDA IND # 125320 and ongoing trials for the use of native
Ang-(1-7) treatment of cognitive impairment in patients with heart failure (HF) or cardiac disease to advance our
2nd-generation glycosylated Ang-(1-7), to complete full regulatory toxicology needed for IND submission and
Phase I safety studies. Our comprehensive University of Arizona and ProNeurogen team of peptide medicinal
chemists, neuroscientists, pharmacologists and drug industry specialists have developed a novel approach to
take advantage of the anti-inflammatory and neuroprotective nature of the G-protein linked Mas receptor and
our extensive experience with Ang-(1-7) agonists. Within the brain, the Mas receptor is expressed on neurons,
microglia and vascular endothelial cells and activation of Mas decreases ROS and brain inflammation, increases
cerebral circulation via increases in endothelial NO release and inhibits hypoxia-inducing factor-1alpha 1,3,17. Our
research team has developed, optimized and completed high-throughput in vitro and in vivo screens of novel
synthetic glycopeptide derivatives of Ang-(1-7) that have outstanding brain penetration and enhanced stability
2,4,6,10,12. We have completed full physiochemical profiling of our lead candidate. With the completion of the Aims
below, we will obtain the protocols and necessary documentation to file a new IND with the FDA to begin clinical
trials for cognitive impairment in patients as risk for developing VCID or ADRD. The diversity supplement will
focus on Specific Aim of the parent application with a focus on the inclusion of menopausal females. The
pertinent specific hypothesis that will be directly addressed by the supplement candidate is as follows:
Hypothesis. The glycosylated Ang 1-7 peptide (PNA5) will significantly improve bio-availability of Ang 1-7 and
increase PNA5 concentration in the brain, in menopausal females, with little to no BBB disruption, who
demonstrate VCID cognitive impairment via activation of the G-protein linked Mas receptor.
 Accordingly, to address the specific hypothesis, the following Specific Aims will be executed:
Aim Ia. Identify Minimal Effective Dose (MED), Optimal Effective Dose (OED) and Optimal Dose
Frequency for native Ang-(1-7) and PNA5 for cognitive protection in menopausal females.
...

## Key facts

- **NIH application ID:** 10271099
- **Project number:** 3U01AG066623-01S2
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Meredith Hay
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $16,031
- **Award type:** 3
- **Project period:** 2020-04-15 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10271099

## Citation

> US National Institutes of Health, RePORTER application 10271099, IND Enabling Studies for a Novel Mas Receptor Agonist for Treatment of Cognitive Impairment in Patients at Risk for Alzheimer's Disease Related Dementia (3U01AG066623-01S2). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10271099. Licensed CC0.

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