# Pilot Study on Novel Compounds for the Prevention of Aging-related diabetic Hyperamylinemia

> **NIH NIH R03** · NORTH CAROLINA CENTRAL UNIVERSITY · 2020 · $74,000

## Abstract

Project Summary
T2D is a chronic metabolic disorder that increases the risk for dementia (including AD). Both
aging-related T2D and AD belong to protein amyloidosis diseases, of which currently there are
no known cures. Our long-term goal is to understand the molecular mechanisms that link T2D
and its complication of neurological deficits and to develop new chemical biology strategies to
prevent and treat amylin amyloidosis based diabetic complications. T2D patients have
increased blood concentrations of amylin, a peptide hormone that is co-secreted with insulin
from pancreatic beta-cells. This hyperamylinemic state makes highly amyloidogenic amylin
hormone more prone to amyloid formation and deposition in the pancreas in T2D patients.
Recent clinical and animal model studies provide strong evidence that amylin amyloid
contributes to neurological symptoms mimicking AD. Therefore neutralizing the toxic amylin
amyloid (without affecting the physiological roles of the monomeric hormone) could be an
effective strategy to prevent and treat amylin amyloidosis. We discovered rosmarinic acid (RA)
from library screening and we further engineered a unique RA analog (RA-amide) that is more
potent than RA in inhibited amylin amyloid formation and reduced amylin amyloid-induced
cytotoxicity against pancreatic beta-cells and neuronal cells. We provide evidence that RA-
amide significantly reduces human amylin oligomers with sera samples taken from HIP rats and
from diabetic patients. We hypothesize that RA-amide will potently inhibits amylin
amyloid/oligomers in the circulation in vivo. To test this hypothesis, we will pursue two Specific
Aims: (1) Determine RA-amide effects on neutralizing amylin amyloid-induced cytotoxicity in
primary neurons and in rat islets. (2) Determine in vivo efficacy of RA-amide in alleviating
human amylin plaque depositions and related pathology including neurobehavioral deficits. This
pilot study serves as proof-of-concept in vivo efficacy tests of RA-amide to collect necessary
data from a humanized rat model for a future R01 project.

## Key facts

- **NIH application ID:** 9863986
- **Project number:** 7R03AG061531-02
- **Recipient organization:** NORTH CAROLINA CENTRAL UNIVERSITY
- **Principal Investigator:** Bin Xu
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $74,000
- **Award type:** 7
- **Project period:** 2019-02-15 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9863986

## Citation

> US National Institutes of Health, RePORTER application 9863986, Pilot Study on Novel Compounds for the Prevention of Aging-related diabetic Hyperamylinemia (7R03AG061531-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9863986. Licensed CC0.

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