Targeting Critical Limb Ischemia Through Modulation of Cox6a2Case # 1605

Technology Contact

A. Carlyle Rogers, PhD
Phone: 252-737-1648


Peripheral artery disease (PAD) is the third leading cause of atherosclerotic cardiovascular mortality, with an estimated age-adjusted prevalence of at least 12% in the United States. Critical limb ischemia (CLI) is the most severe form of peripheral arterial disease (PAD), and carries a substantially high morbidity and mortality rate. Further, CLI patients have a risk of major amputation or death that approaches 40% in the first year of diagnosis.


Dr. Joseph McClung from the Department of Physiology has discovered that mitochondrial mechanisms by which limb muscle cells respond to ischemia and influence the limb vasculature in PAD may represent a new strategy to prevent tissue loss and subsequent limb amputation in patients with CLI. Specifically, modulation of oxidiative and/or glycolytic metabolism by delivery of Cox6a2 to ischemic muscle tissue may hold the key to improving limb muscle mitochondrial respiration and protecting the vascular network. Preliminary data in a mouse model of ischemia demonstrates that Cox6a2 protein abundance is in-part required for protection from ischemic mitochondriopathy and therapeutic re-expression is sufficient to alleviate ischemic pathology. Further, re-expression of Cox6a2 during ischemia rescues mitochondriopathy and regenerative myopathy in CLI In human primary muscle cells.


  • Peripheral Artery Disease 
  • Critical Limb Ischemia 
  • Acute Limb Ischemia 
  • Intermittent Claudication 

Selected Publication

Schmidt CA, Ryan TE, Lin CT, Inigo MMR, Green TD, Brault JJ, Spangenburg EE, McClung JM; Diminished force production and mitochondrial respiratory deficits are strain-dependent myopathies of subacute limb ischemia. J Vasc Surg. 2017 May;65(5):1504-1514.e11. PMID:  28024849