# 3D High Throughput Model to Predict Drug Efficacy in Fibrosis Progression vs Reversal

> **NIH NIH R21** · GEORGIA INSTITUTE OF TECHNOLOGY · 2020 · $234,976

## Abstract

ABSTRACT: 3D High Throughput Model to Predict Drug Efficacy in Fibrosis Progression vs Reversal
Idiopathic pulmonary fibrosis (IPF) is the most relentlessly progressive and fatal fibrotic lung disorder, which
disproportionately affects the elderly. Although two drugs have recently gained FDA-approval for IPF, these
drugs only moderately slow the progression of lung decline and do not improve quality of life for patients.
There are no available therapies that can `reverse' fibrosis. Despite efforts by numerous groups to develop
IPF treatments, progress has been aggravatingly slow. This proposal focuses on two possible reasons for
these difficulties: (1) Current pre-clinical screening models fail to reliably predict the success of drug
candidates in humans, and (2) Although IPF is widely regarded as an age-related disease, drug treatments
have not targeted age-associated pathologic mechanisms.
The existing paradigm, that pathologic fibrosis is a “fibro-proliferative” process, has not led to effective IPF
treatments. This proposal integrates expertise in fibroblast aging and novel IPF therapeutics in development
(Hecker lab) with cutting edge technologies for microscale bioprinting and 3D cell assays (Takayama lab) to
develop a high throughput phenotypic cellular screening assay to determine efficacy for fibrosis reversal. The
proposed studies will utilize normal “control”, aged “senescent”, and IPF human lung fibroblasts in small
numbers to bioengineer a high-throughput phenotypic assay that will evaluate fibrosis over a 21 day period.
An aqueous two phase system (ATPS) bioprinting of these cells will be used to create microscale contraction
assays that are several order of magnitude smaller in volume compared to conventional assays. Importantly,
the project will repeatedly micro-print fresh collagen around already contracted cell-laden gels to enable
repeated contractions over 21 days. The proposed model will enable the first high-throughput phenotypic
screening assay with the capability to determine a drug candidate's efficacy for fibrosis progression and
reversal. The new cellular assay will be validated for its ability to identify fibrosis reversal drugs using
“Noxindoline” a highly selective Nox4 inhibitor that is currently in preclinical development by the Hecker lab.
Noxindoline was identified by the Hecker lab through studies of age-dependent alterations in Nox4 that
results in a sustained redox imbalance, and promotes senescence and apoptosis-resistance of
myofibroblasts. The proposal hypothesizes that current therapies (Nintedanib and Pirfenidone) will inhibit the
progression of pro-fibrotic phenotypes (but not reversal), whereas treatment with Noxindoline will promote
the reversal of established pro-fibrotic phenotypes. The aims are:
Aim1: Develop high throughput bioprinted cellular assay for fibrosis progression using non-senescent cells
Aim2: Monitor fibrosis progression and reversal of senescent cells and IPF patient cells

## Key facts

- **NIH application ID:** 9975675
- **Project number:** 5R21AG061687-02
- **Recipient organization:** GEORGIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** LOUISE HECKER
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $234,976
- **Award type:** 5
- **Project period:** 2019-07-15 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9975675

## Citation

> US National Institutes of Health, RePORTER application 9975675, 3D High Throughput Model to Predict Drug Efficacy in Fibrosis Progression vs Reversal (5R21AG061687-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9975675. Licensed CC0.

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