# Extended-Release Formulation of Mas Receptor Agonists as Novel Therapeutics for Treating Cognitive Impairment in Patients at-risk forAlzheimer's Disease-Related Dementias and Vascular Dementia

> **NIH NIH R43** · PRONEUROGEN, INC. · 2022 · $499,763

## Abstract

Vascular contributions to cognitive impairment and dementia (VCID) and Alzheimer’s disease related dementias
(ADRD) significantly contribute to the 47 million people world-wide who suffer with dementia. This number is
estimated to increase to over 130 million people by 2050. Several studies have shown that VCID and conversion
to ADRD are strongly correlated with vascular disease, inflammation and decreased cerebral brain blood flow.
The relationship between vascular disease, cognitive function and progression to dementia and possible AD
have been recently reviewed 1. These authors successfully make the case for a close relationship between
cardiovascular risk factors and risk for VCID and ADRD. Furthermore, conversion rates of VCID to dementia
has been reported to be within 40-46% within 5 years of diagnosis of VCID. To date, there are no approved
therapies for VCID. ProNeurogen has been working to develop novel Angiotensin 1-7 (Ang-1–7) formulations to
treat cognitive impairment in patients at for risk ADRD and VCID. The goal of the present SBIR Phase I project
is to advance the development of extended-release (ER) subcutaneous injection formulation for the
administration of our novel peptide therapy, PNA5, for VCID. These novel peptide formulations are designed
to act on Mas receptors (MasR) within the brain vascular endothelium, neuronal cells and microglia to decrease
brain reactive oxygen (ROS) production and neuroinflammation. We have begun to translate these preclinical
findings into novel peptide therapeutics to treat cognitive impairment in patients with heart disease who are at
risk for ADRD or VCID. With support from NIA, we are currently completing our formal IND enabling toxicology
studies required to advance PNA5 to human clinical trials for VCID and expect to submit our IND application by
Q1 2023. Our current planned treatment protocol for VCID patients is once a day, subcutaneous 100 microg/kg
injection using a standard needle and syringe for 85 days. However, to increase patient compliance as well as
accelerate commercialization we are currently investigating new formulations that are more patient friendly and
require fewer injections. We will take advantage of Drug Delivery Experts LLC (now Pace Labs) extensive
experience in the formulation of poly(lactic-co-glycolic acid) (PLGA) sterile injectable in-situ gel formulations and
manufacturing expertise to complete the 2 principal objectives of this project.
Objective 1: Complete formulation development and scale up batch manufacturing of our extended-
release in-situ gel injection formulation of PNA5.
Objective 2. Complete in vivo PK studies of the extended-release injection formulations and compare to
standard saline formulations of PNA5.
Following successful completion of these feasibility studies, in Phase II we will conduct extensive PD/PK
studies of the PNA5-PLGA formulation in our VCID animal model to establish the cognitive protective and anti-
inflammatory effects of PNA5-...

## Key facts

- **NIH application ID:** 10594875
- **Project number:** 1R43AG077967-01A1
- **Recipient organization:** PRONEUROGEN, INC.
- **Principal Investigator:** Meredith Hay
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $499,763
- **Award type:** 1
- **Project period:** 2022-09-30 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10594875

## Citation

> US National Institutes of Health, RePORTER application 10594875, Extended-Release Formulation of Mas Receptor Agonists as Novel Therapeutics for Treating Cognitive Impairment in Patients at-risk forAlzheimer's Disease-Related Dementias and Vascular Dementia (1R43AG077967-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10594875. Licensed CC0.

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