# MitoQ treatment of claudication: myofiber and micro-vessel pathology

> **NIH NIH R01** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2022 · $631,128

## Abstract

Abstract
Claudication, the most common clinical presentation of patients with Peripheral Artery Disease (PAD), is a
severe functional limitation of the lower extremities identified as walking-induced leg muscle pain relieved by
rest. Numerous studies have identified a lower-leg myopathy in these patients. There is general agreement
that the proximate cause of this myopathy is dysfunctional mitochondria which produce oxidative damage in
response to repeated episodes of walking-induced ischemia/hypoxia. These patients have few therapeutic
options including only two FDA approved medications, Pentoxifylline and Cilostazol, which are modestly
effective. A promising medication for treatment of claudicating PAD patients is MitoQ an antioxidant that
concentrates several hundred-fold in mitochondria. The significant contribution of mitochondrial oxidative
damage to a wide range of pathologic conditions has stimulated clinical studies which have found MitoQ to be
safe and effective. Our group has documented improved walking performance of claudicating PAD patients
receiving a single dose of MitoQ. We propose to study, for the first time, the effects of long-term MitoQ
treatment on the myopathy and functional performance of claudicating PAD patients. Our Hypothesis:
Treatment of claudicating PAD patients with MitoQ for six months improves 1) patient performance determined
as walking performance, daily physical activity, and quality of life, 2) calf muscle histopathology and
pathophysiology, and 3) the systemic physiological parameters pulmonary O2 uptake (VO2) and metabolic
profile. These changes correlate directly with reduced oxidative damage to calf muscle mitochondria, improved
mitophagy, and improved mitochondrial function. We will test this hypothesis by implementing the following
Specific Aims. Specific Aim ‘1’ will test the hypothesis that a six-month regimen of MitoQ improves
performance determined as walking performance, daily physical activity, and quality of life of claudicating PAD
patients, in association with improved calf muscle histopathology & pathophysiology, and improved VO2 &
systemic metabolic profile. Specific Aim ‘2’ will test the hypothesis that a six-month regimen of MitoQ reduces
mitochondrial oxidative damage, improves mitophagy, and improves mitochondrial function of the voluminous,
myofiber-mitochondrial compartment and that these improvements correlate with improved performance of
claudicating PAD patients, improved calf muscle histopathology & pathophysiology, and improved VO2 &
systemic metabolic profile. Specific Aim ‘3’ will test the hypothesis that a six-month regimen of MitoQ
improves endothelial function and lower extremity hemodynamics, calf muscle heme oxygenation, and
endothelium-dependent vasomotor function of micro-vessels isolated from the affected calf muscle of
claudicating PAD patients, in association with improved mitochondrial function of the micro-vessels.
 If our hypothesis is correct, the work will support...

## Key facts

- **NIH application ID:** 10608773
- **Project number:** 1R01AG077803-01A1
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** George Pasco Casale
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $631,128
- **Award type:** 1
- **Project period:** 2022-09-30 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10608773

## Citation

> US National Institutes of Health, RePORTER application 10608773, MitoQ treatment of claudication: myofiber and micro-vessel pathology (1R01AG077803-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10608773. Licensed CC0.

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