# Anti-inflammatory and Anti-diabetic Therapy for Metabolic Syndrome

> **NIH NIH R43** · APT THERAPEUTICS, INC. · 2020 · $300,000

## Abstract

Principal Investigator/Program Director (Last, First, Middle: Chen, Ridong
Abstract
 Metabolic syndrome (MetS), affects more than 50 million people in the US alone. The current standard of
care embodies polypharmacological therapies that are mostly directed at controlling individual risk factors of
MetS (e.g. lipid altering agents, anti-hypertensives, and insulin sensitizers), but most of these treatments do not
target underlying pathological mechanisms. Consequently, there is high unmet need to develop an innovative
therapy that ultimately prevents cardiovascular morbidity and mortality by targeting major pathophysiological
mechanisms, normalizing or improving metabolic syndrome risk factors, and reversing type 2 diabetes (T2D).
CD4+CD25+Foxp3+ regulatory T cells (Treg) modulate inflammation and insulin resistance. Treg cells are highly
enriched in the visceral adipose tissue (VAT) of normal animals, but their numbers are reduced in insulin-resistant
models of obese animals. Importantly, decreased numbers of Tregs are also found in obese human omentum.
 Interleukin-2 (IL-2) is the key cytokine for the generation, survival, and function of Tregs by direct binding to its
high affinity receptor. Treatment with low-dose (1-3% cancer model dose) rIL-2 increases anti-inflammatory Treg
cells and M2 type macrophages and inhibits pathogenic interferon- secreting T helper type 1 cells in the
abdominal fat, leading to improvement in glucose tolerance and insulin sensitivity in mice on a high fat diet.
Moreover, IL2 turns unhealthy white fat into beneficial brown fat. Hence, restoration of VAT Treg cells and
“browning” with low-dose IL-2 may offer a novel strategy for prevention and treatment of T2D and the reduction
of cardiovascular disease. However, several drawbacks exist for current low-dose rIL-2 therapy, including a short
half-life, propensity to in vitro aggregation causing adverse local reaction at injection sites, and a potentially
narrow therapeutic window. We have designed a proprietary IL-2 fusion therapy with multiple functions and a
broad therapeutic window. In the proposed Phase I SBIR study, we will determine whether weekly treatment of
the fusion therapy for 12 weeks will effectively reverse the major risk factors of MetS and type 2 diabetes in
ZDSD rats continuously fed a high fat and carbohydrate diet. The long-term goal of this project is to develop an
innovative and global treatment for MetS and diabetes.

## Key facts

- **NIH application ID:** 10152145
- **Project number:** 1R43DK126493-01A1
- **Recipient organization:** APT THERAPEUTICS, INC.
- **Principal Investigator:** RIDONG CHEN
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $300,000
- **Award type:** 1
- **Project period:** 2020-09-15 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10152145

## Citation

> US National Institutes of Health, RePORTER application 10152145, Anti-inflammatory and Anti-diabetic Therapy for Metabolic Syndrome (1R43DK126493-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10152145. Licensed CC0.

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