# Human on a chip systems to investigate disease comorbidities common in the aged population

> **NIH NIH R44** · HESPEROS, LLC · 2020 · $1,483,966

## Abstract

Project Summary
 Both older adults and the pharmaceutical industry would benefit from the development of human-on-a-chip
systems to be able to systematically investigate disease comorbidities and their response to drug candidates in
the aged population at the preclinical stage due to the lack of good multimodal models of disease
combinations. We will investigate diseases that are most prevalent in the aged population including non-
alcoholic fatty liver disease (NAFLD), cardiomyopathy, cachexia/sarcopenia and type II diabetes. The influence
of metabolic diseases, especially type II diabetes, on aged and diseased patients is well known, but little
studied at the preclinical level. This proposal will build upon the expertise at Hesperos and their current
collaborations with UCF and the Center for Pharmacodynamics at the University of Florida branch, located in
Orlando. We will use Hesperos’ patented multi-organ functional systems to investigate multiple disease
phenotypes to determine how other deficits in organs or modalities enhance or cause disease, hasten
progression or limit treatment options in each organ. It is also unclear how normal aging is affected by
metabolic disorders, although some correlations have been observed. Human-on-a-chip models composed of
multiple organs in recirculating media will provide a controlled reproducible system to evaluate responses to
drugs. In addition, by comparing acute to chronic effects, the model will enable prediction of clinical trial
success using models to inform clinical disease trial design based on these preclinical studies.
 We will build on ongoing initiatives to expand PBPK/PD modeling and simulation platforms to geriatrics by
accounting for changes in the underlying pathophysiology with age. These models may also serve as
screening tools during early stages of drug development and facilitate decision-making with respect to
selecting the compound with a more favorable PK and formulation properties. To construct a well-defined
system, we will use a common serum free medium with functional readouts using microelectrode arrays and
cantilevers that are integrated on chip that allow for noninvasive electronic and mechanical readouts for acute
drug responses in Phase I and chronic drug tests in Phase II. The Phase I portion of this proposal will show
that three organs can be linked together - liver, cardiac and muscle- and that their response to therapeutics
can reproduce responses in clinical trials. Drug and drug combinations will then be tested in the multiplexed
disease models acutely for altered efficacy and toxicity compared to healthy or non-comorbidity systems. After
the quantitative milestones for Phase I have been achieved, the acute studies will be extended to chronic
applications in Phase II. We will also establish a type II diabetic phenotype in the system by utilizing different
concentrations of insulin and glucose in a five-organ system developed by integrating the system in Aim 1 with
a...

## Key facts

- **NIH application ID:** 10137643
- **Project number:** 4R44AG059511-03
- **Recipient organization:** HESPEROS, LLC
- **Principal Investigator:** James J Hickman
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,483,966
- **Award type:** 4N
- **Project period:** 2018-04-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10137643

## Citation

> US National Institutes of Health, RePORTER application 10137643, Human on a chip systems to investigate disease comorbidities common in the aged population (4R44AG059511-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10137643. Licensed CC0.

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