Mitoq treatment of claudication: myofiber and micro-vessel pathology

Active Project Grant Awarded Last action

Award ID
R01AG077803
Recipient
Awarding agency
Obligated
$4,195,836

Award facts

Assistance listing
93.866 Aging Research
Completion date 87% complete
Place of performance
Omaha, NE 68198, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

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 a causal connection between mitochondrial oxidative damage and pad myopathy and patient performance; and identify mitoq as a promising treatment for pad.

Transactions

Action Obligated Date
Amendment $577,740
Amendment $566,185
Amendment $595,289
Amendment $0
Amendment $597,183
Amendment $597,183
Amendment $0
Amendment $0
Amendment $0
Amendment $0
Amendment $0
Amendment $0
Amendment $0
Amendment $631,128
Original award $631,128
Show all 15

Subawards

Subrecipient Amount Awarded
Nebraska Educational Biomedical Research Association MitoQ treatment of claudication: myofiber and micro-vessel pathology $59,447
University Of Nebraska $85,546
University Of West Florida $112,400
University Of Nebraska $87,292
Nebraska Educational Biomedical Research Association $59,120
Nebraska Educational Biomedical Research Association $59,120
Nebraska Educational Biomedical Research Association MitoQ Treatment $57,003

Quick answers

Who received award R01AG077803?

R01AG077803 was awarded to Board Of Regents Of The University Of Nebraska by National Institute on Aging (National Institutes of Health) on September 30, 2022.

How much is award R01AG077803 worth?

$4,195,836 has been obligated on R01AG077803.

On GovTribe

See this award's full record

  • Every transaction and subaward
  • The recipient's other awards and teaming partners
  • Similar grant awards
  • Ask GovTribe AI about this award
Try for free Login