# Evaluation of a selective PPAR-gamma agonist for treatment of Alzheimer’s Disease

> **NIH NIH R43** · OLEOLIVE, INC. · 2020 · $103,008

## Abstract

PROJECT SUMMARY
Alzheimer’s disease (AD) is the sixth leading cause of death in United States, yet this indication lacks truly
effective therapeutics to mitigate this disease. To address this problem, a novel (partial) peroxisomal
proliferator activating–gamma (PPAR) nuclear receptor agonist (AU-9) that has selective amino acid
interactions in the receptor ligand-binding domain was developed. Preliminary data suggest AU-9 may reduce
AD-related pathologies, including amyloid accumulation, neuro-inflammation, behavioral deficits and
neurodegeneration (reduced neuronal plasticity). The goal of this current application is to further test and
develop AU-9 in preparation to submit an IND application to the FDA to initiate clinical trials. Two aims are
proposed to achieve this goal. Aim 1 will evaluate the effective concentration, absorption and distribution of
AU-9 in rodent models of Alzheimer’s disease. The minimal concentration of AU-9 needed to improve neuronal
plasticity will be determined by electrophysiological analysis. Maximum tolerated doses will also be assessed.
Live-cell in vitro imaging will be used to validate preliminary data, support in vivo findings proposed herein and
gain mechanistic insight to AU-9 effects. Finally, pharmacokinetic analysis and tissue distribution of AU-9 using
LC-MS analysis will be performed in a dose and time dependent manner. Aim 2 will evaluate the safety of AU-
9 following long-term treatment in mice. Current full PPAR agonists produce unwanted side effects on the
heart and liver. Potential adverse reactions of AU-9 will be observed (testing over a range of doses over 6
months) on both the heart and liver, organs normally adversely impacted with current clinical PPAR agonists.
In addition, this aim will focus on key IND enabling data required by FDA guidelines, including measuring the
effects of AU-9 on liver enzyme levels (CYP enzymes). The results of these studies are expected to confirm
AU-9 as a potential treatment or preventive therapy for AD and ultimately support efforts to submit an IND
application and initiate Phase I clinical trials testing AU-9.

## Key facts

- **NIH application ID:** 9998828
- **Project number:** 5R43AG065069-02
- **Recipient organization:** OLEOLIVE, INC.
- **Principal Investigator:** JAMES CARDELLI
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $103,008
- **Award type:** 5
- **Project period:** 2019-09-01 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9998828

## Citation

> US National Institutes of Health, RePORTER application 9998828, Evaluation of a selective PPAR-gamma agonist for treatment of Alzheimer’s Disease (5R43AG065069-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9998828. Licensed CC0.

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