# Mitoprotective therapy for treatment of ankle PTOA

> **NIH NIH R01** · CORNELL UNIVERSITY · 2020 · $489,030

## Abstract

Project Summary Abstract
Post-traumatic osteoarthritis (PTOA) frequently develops secondary to joint injury, with clinical manifestations
of pain and dysfunction lagging months to years after the injury. No effective therapies exist to prevent or slow
PTOA progression, and evidence indicates interventions must occur acutely after injury to modify the disease
course. The novel peptide SS-31 is a highly targeted mitoprotective therapy that has shown success in clinical
trials for treatment of several diseases. This project will test the hypothesis that acute mechanical trauma
induces MT dysfunction in chondrocytes that leads to PTOA, and that restoring MT bioenergetics with SS-31
will arrest the development of PTOA in vivo. First, the early (seconds to days) temporal response of cartilage to
injury with respect to MT function, cell death, and matrix degradation, will be assessed to identify a therapeutic
window of time for treatment of MT dysfunction after mechanical injury of cartilage. Then, the efficacy of SS-31
in mitigating the effects of cartilage injury will be studied to identify the time course in which mitoprotection can
effectively inhibit MT dysfunction, restore cellular bioenergetics and prevent cell death. Finally, the effects of
mitochondrial stabilization on PTOA in vivo will be assessed in the peracute to chronic phases following
impact-induced cartilage damage and MT dysfunction in vivo. The results of these studies will demonstrate if
mitoprotective therapies restore mitochondrial bioenergetics, prevent acute cell injury and apoptosis, and
inhibit the progression of cartilage degeneration, thereby providing the first therapy to prevent PTOA. All
components of this proposal reflect and support the mission of the National Institute of Arthritis and
Musculoskeletal and Skin Diseases. Completion of the proposed project will reveal novel scientific information
about the early changes in cartilage at subcellular to macroscopic resolution scales after injury. Understanding
the acute post-injury pathobiology of PTOA is critical because it represents a time point where true
intervention, with an aim at preventing PTOA, is possible before the disease becomes fully established. The
success of SS-31 in several phase II clinical trials, where disease is already established, suggests that
mitoprotection will also be an effective therapy for PTOA in those cases where OA is present at the time of
diagnosis and treatment. Two PhD students will be trained in this proposal with input from a multifaceted
interdisciplinary team of scientists and clinicians from the human clinical and animal models perspectives.
Finally, all members of the assembled team in this proposal are well represented on national and international
levels in their respective fields, and they are dedicated and experienced at dissemination of scientific
information at meetings and in journal publications. The interdisciplinary team assembled for this project has
an established col...

## Key facts

- **NIH application ID:** 10003816
- **Project number:** 5R01AR071394-04
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** LISA A FORTIER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $489,030
- **Award type:** 5
- **Project period:** 2017-09-22 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10003816

## Citation

> US National Institutes of Health, RePORTER application 10003816, Mitoprotective therapy for treatment of ankle PTOA (5R01AR071394-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10003816. Licensed CC0.

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