# Biologics for Improved Aged Muscle Function

> **NIH NIH R43** · JUVENA THERAPEUTICS INC · 2021 · $254,262

## Abstract

ABSTRACT
 Sarcopenia is the disease of muscle wasting and loss of strength associated with aging. This disease
afflicts 10-25% of those over age 65, increasing > 50% of those over age 80. While debilitating in its own right,
muscle weakness is a major risk factor for fall injury and increases the risk of resulting disability up to 4.6-fold,
resulting in an immense healthcare burden to society. 1 in 4 Americans over the age of 65 suffers a fall every
year, leading to over 8 million cases requiring medical care annually, the direct costs of which exceed $50
billion to the US healthcare system. Thus, developing therapeutics to treat and reverse sarcopenia will be
essential for preventing the frequent spiral into disability after injury in the elderly. While the CDC recognized
sarcopenia as a reimbursable clinical indication in 2016, unfortunately, there are 0 FDA approved therapeutics
available today, as no drug candidates have demonstrated both safety and efficacy. Using a proprietary
ML-enabled high-throughput screening platform, Juvena Therapeutics has identified several signaling proteins
secreted by human embryonic stem cells that ameliorate key cellular aspects of sarcopenia in aged muscle
fibers and progenitor cells. In pilot studies, systemic or local administration of these proteins in sarcopenic,
aged mice improved muscle strength and fiber size, and enhanced the regenerative capability of "aged"
muscle stem cells. This Phase I will focus on developing variants of two of the lead candidates modified to
achieve a target product profile with extended stability and wider therapeutic window required for effective
clinical use and product commercialization. In Aim 1, we will: (1) add stabilization motifs to modulate stability,
extending half-lives from minutes to >96 hours; (2) confirm that the engineered variants maintain their
regenerative properties in aged mouse and human myoblasts using validated in vitro injury-activate models of
skeletal muscle regeneration; and (3) conduct pilot PK studies using 2 routes of administration (s.c. and i.v.) to
inform Aim 2 in vivo efficacy studies. In Aim 2, efficacy of the modified lead candidates will be assessed in a
natural sarcopenia model using aged mice. Success will be indicated by demonstrating the lead biologic
produces an improvement in maximal or sustained muscle force production (strength and endurance) as a
statistically significant increase in grip strength, treadmill performance, in vivo and in situ direct muscle
stimulation and force measurement, improvements in muscle fiber size and reduced fibrosis. Once feasibility is
demonstrated, Phase II will focus on large-scale, GMP production of sufficient material to carry out CMC,
Safety/tox for IND enabling studies as well as in vivo efficacy studies. In the long term, we will expand the
therapeutic applications for our regenerative proteins to include other indications associated with stem cell
dysregulation with aging such as acute injury / p...

## Key facts

- **NIH application ID:** 10323586
- **Project number:** 1R43AG071181-01A1
- **Recipient organization:** JUVENA THERAPEUTICS INC
- **Principal Investigator:** Jeremy O'Connell
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $254,262
- **Award type:** 1
- **Project period:** 2021-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10323586

## Citation

> US National Institutes of Health, RePORTER application 10323586, Biologics for Improved Aged Muscle Function (1R43AG071181-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10323586. Licensed CC0.

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