# Combining Prostaglandin E2 Modulation and Rehabilitation for Treatment of Volumetric Muscle Loss

> **NIH VA I21** · VETERANS ADMIN PALO ALTO HEALTH CARE SYS · 2024 · —

## Abstract

The aging population accounts for nearly 50% Veterans, but only 18% of non-Veterans. This large population
of aging Veterans is susceptible to age-related skeletal muscle wasting known as sarcopenia. Importantly, there
are no FDA-approved drugs for treating sarcopenia. Consequently, identifying cost-effective interventions to
treat sarcopenia is a major public health challenge for Veterans. At the cellular level, one of the important
contributors of sarcopenia is dysfunction of the satellite cells or muscle progenitor cells (MPCs), leading to the
impaired ability to form new muscle fibers. Physiologically, muscle-derived prostaglandin E2 (PGE2) is an
important inducer of myogenesis by activating the expansion of satellite cells and MPCs that precedes muscle
formation. However, owing to PGE2's rapid degradation in vivo, one strategy to increase the abundance of
PGE2 is to block the negative regulator of PGE2 known as prostaglandin E2 (PGE2)-degrading enzyme (15-
PGDH). Through our previous space-based drug screening studies aboard the International Space Station to
study muscle formation using engineered muscle tissue, we identified a small molecule inhibitor of 15-PGDH
(SW033291) that has profound effect in enhancing muscle formation in vitro. However, successful clinical
translation of this drug will require site-specific and sustained delivery of SW03329. Furthermore, since exercise
is recommended to combat sarcopenia, the potential synergistic benefits of drug therapy and exercise have yet
to be evaluated. Therefore, the objective is to develop a biomaterials-based strategy for site-specific and
sustained release of SW033291, and then to test the efficacy of drug delivery with rehabilitative exercise for
treating sarcopenia in aged mice. The overarching hypothesis is that biomaterials-based delivery of SW03329
with rehabilitative exercise will improve muscle function and muscle mass in a murine sarcopenia model. Specific
Aim 1 is to develop a microsphere-based sustained release system for SW033291, and to validate the efficacy
of SW033291 to promote muscle formation and contractility in vitro. We hypothesize that the biocompatible
microspheres will support sustained drug release, leading to enhanced muscle formation in MPCs. We will
employ an established poly(lactic-co-glycolic acid)-poly(ethylene glycol)-carboxyl (PLGA-PEG-COOH)-based
microsphere delivery system to achieve a range of sustained release concentrations. MPCs will be cultured in
expansion media for 5 days either in the presence or absence of the drug-laded microspheres. For up to 5 days
after exposure to the microspheres, MPCs will be assessed for cell cytotoxicity, and the conditioned media will
be assayed for PGE2 levels using a PGE2 enzyme linked immunosorbent assay. To study the efficacy of drug
exposure on myotube formation, the cells will be immunofluorescently stained to visualize myotubes using
skeletal muscle myosin heavy chain. The degree of myotube contractility in res...

## Key facts

- **NIH application ID:** 10925078
- **Project number:** 1I21RX004898-01A1
- **Recipient organization:** VETERANS ADMIN PALO ALTO HEALTH CARE SYS
- **Principal Investigator:** Ngan F. Huang
- **Activity code:** I21 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2024-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10925078

## Citation

> US National Institutes of Health, RePORTER application 10925078, Combining Prostaglandin E2 Modulation and Rehabilitation for Treatment of Volumetric Muscle Loss (1I21RX004898-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10925078. Licensed CC0.

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