# Improved carnosic acid congener compounds for Alzheimer’s disease

> **NIH NIH R43** · LARIX BIOSCIENCE, LLC · 2022 · $326,205

## Abstract

Improved carnosic acid congener compounds for Alzheimer’s disease
Abstract
 Five million Americans currently suffer the devastating consequences of Alzheimer’s disease (AD), and
unfortunately, the numbers are increasing due to our aging population. While some treatments can lower disease
burden, there is no cure and all patients inevitably succumb. Cost of care for treatment of AD is expected to
reach $1.1 trillion without an effective treatment or a change in the trajectory of AD. Loss of synaptic function is
associated with cognitive decline in AD and is a better predictor of cognitive loss in AD than plaques or tangles.
Damage to neurons occurs at least partially through generation of oxidative and nitrosative stress, due to
excessive generation of reactive oxygen/nitrogen species (ROS/RNS) triggered by oligomeric amyloid beta (Aβ)
peptide and downstream hyperphosphorylation and aggregation of tau protein (pTau). Carnosic acid (CA), a
phenolic diterpene particularly abundant in the herb rosemary (Rosmarinus officinalis), protects neurons and
synapses from damage caused by oxidative stress. In addition to direct antioxidant activity, CA belongs to a
class of “pro-electrophiles” that activate the Keap1/Nrf2 pathway, upregulating transcription of a broad range of
phase II antioxidant and anti-inflammatory proteins through the antioxidant responsive element (ARE). In vitro,
CA protects neurons from Aβ toxicity. CA treatment ameliorates various behavioral and histological deficits in
transgenic AD model mice, while showing no significant side effects. During this Phase 1 project, we will develop
a novel, proprietary CA-derived therapeutic with improved bioavailability to achieve therapeutic levels
with once daily dosing. We will then evaluate this novel compound as a therapeutic small molecule for the
treatment of AD.

## Key facts

- **NIH application ID:** 10601159
- **Project number:** 1R43AG080911-01
- **Recipient organization:** LARIX BIOSCIENCE, LLC
- **Principal Investigator:** JAMES W LARRICK
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $326,205
- **Award type:** 1
- **Project period:** 2022-09-30 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10601159

## Citation

> US National Institutes of Health, RePORTER application 10601159, Improved carnosic acid congener compounds for Alzheimer’s disease (1R43AG080911-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10601159. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*