# Macrophage targeted microparticles for the regeneration of atrophied muscle

> **NIH VA I01** · VETERANS HEALTH ADMINISTRATION · 2024 · —

## Abstract

PROJECT SUMMARY: Muscle weakness in VA patients most commonly results from inactivity related to injury,
illness, or surgery. Even with aggressive rehabilitation, bouts of enforced skeletal muscle inactivity can lead to
atrophy and loss of function that persist long after remobilization. While pharmacotherapies might improve
outcomes for many veterans suffering from loss of function secondary to disuse atrophy, none exist. Since age-
related loss of muscle function accelerates further loss of function and increases risk of disability, development
of a pharmacotherapy that enables full recovery of function would be transformative for veterans and the general
population. Effective recovery of atrophied skeletal muscle is dependent upon macrophages. First, macrophage
inflammation directs satellite cells to fuse with damaged fibers to facilitate repair. Then, macrophage regenerative
factors resolve inflammation and promote muscle growth. Therefore, a pharmacotherapy is needed that can
specifically target these cells within the skeletal muscle. We met this challenge by developing polymer particles
for localized, extended release of all-trans retinoic acid (ATRA-PLG). ATRA is in broad use clinically for
indications other than muscle wasting, but our data indicate delivery of ATRA-PLG to the facia of atrophied
muscle restores muscle fiber size, improves mobility, increases IGF-1, and decreases IL-6 in the early phase of
recovery. Also, in vitro studies indicate ATRA-PLG induces macrophages to secrete IGF-1. Therefore, our central
hypothesis is that administration of ATRA-PLG to atrophied muscle enhances 1) skeletal muscle recovery and
2) the macrophage regenerative response. We will test this hypothesis by inducing muscle atrophy with cast
immobilization in mice and then injecting ATRA-PLG with release kinetics that match the time course of muscle
recovery when the cast is removed. Specific Aim 1 will determine if ATRA-PLG delivery accelerates functional
recovery of skeletal muscle after remobilization. Specific Aim 2 will determine if ATRA-PLG delivery enhances
the macrophage regenerative response in skeletal muscle recovering from disuse. The potential of this work for
positive impact is high. A pharmacotherapy that enables full functional recovery of atrophied muscle could
revolutionize healthcare for veterans and the general population. If we are successful in rodents, the pathway to
clinical implementation is clear and straight forward. First, our therapy could be tested in large animals using
ultrasound-guided delivery, which is already used in humans for localized musculoskeletal interventions. Second,
ATRA is one of the most prescribed medications in the U.S. and PLG is implemented in 19 FDA drug
formulations. Thus, if ATRA-PLG is successful, getting this therapy to veterans may be faster and less expensive
than developing new drugs. Finally, the delivery system is versatile, able to accommodate new or additional
pharmaceutics or multiple admini...

## Key facts

- **NIH application ID:** 10864778
- **Project number:** 1I01RX004564-01A2
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** Robert Michael Gower
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2024-05-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10864778

## Citation

> US National Institutes of Health, RePORTER application 10864778, Macrophage targeted microparticles for the regeneration of atrophied muscle (1I01RX004564-01A2). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10864778. Licensed CC0.

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