A team of researchers at the University of Virginia School of Medicine will examine whether peripheral arterial disease, a common circulation problem, can be treated with an existing drug compound developed for another purpose.
The work is being funded by the National Institutes of Health, which announced the award June 18. U.Va. is one of nine academic research groups that will share $12.7 million in NIH funding.

“We are delighted to receive this highly competitive award,” said Dr. Brian H. Annex, division chief of cardiovascular medicine at U.Va. and the principal investigator for the grant. “We have the opportunity to rapidly determine the ability of this investigational agent to improve the primary problem of reduced blood flow to the legs, which afflicts millions of patients with peripheral arterial disease.” 



Speeding New Treatments


The NIH has tasked the U.Va. researchers with evaluating the drug zibotentan, manufactured by AstraZeneca, to determine its effectiveness against peripheral arterial disease, or PAD. Dubbed “Discovering New Therapeutic Uses for Existing Molecules,” the pilot initiative is led by the National Center for Advancing Translational Sciences.



This is the first series of awards in the pilot program, which was established to identify new uses for molecules that already have gone through significant safety testing in humans for other indications. The goal is to speed the development of new treatments by harnessing the unknown potential of compounds that have gone through major steps in the development process.



“Innovative, collaborative approaches that improve the therapeutic pipeline are crucial for success,” said NIH director Dr. Francis S. Collins. “This unique collaboration between academia and industry holds the promise of trimming years from the long and expensive process of drug development.”



Other academic institutions receiving awards include Yale, the Mayo Clinic, Baylor College of Medicine and Virginia Commonwealth University. Details on the selected projects are available here.

In addition to AstraZeneca, industry participants in the pilot effort include AbbVie, Bristol-Myers Squibb Co., Eli Lilly and Co., GlaxoSmithKline, Janssen Pharmaceutical Research & Development LLC, Pfizer and Sanofi. 



About Peripheral Arterial Disease


Peripheral arterial disease is a circulation problem that already affects more than 8 million Americans, and that number is expected to rise sharply in coming years. The condition is a complication of atherosclerosis that results from the build-up of cholesterol, fat and clotted blood in the arteries that carry blood to one or both legs. Because of the impeded blood flow, people with PAD can experience leg pain, difficulty walking and other symptoms. More severe cases can result in skin ulcers and even require amputation. 



Existing treatments for the condition, such as cholesterol-lowering drugs, aspirin and blood-pressure medications, cannot improve blood flow to the legs. U.Va. will conduct an imaging study using a method developed primarily at U.Va. to determine if the drug zibotentan can address the fundamental blood-flow problem.



“We have a fabulous interdisciplinary team at U.Va., and this study will use a state-of-the-art, noninvasive imaging test which was largely developed by Dr. Christopher Kramer [co-investigator on the NIH grant] here at U.Va.,” Annex said. “In short, we will directly determine if this drug can address the primary problem in PAD, which is reduced blood flow. The investigational drug might relieve leg pain, help patients walk further and longer, and reduce the costs of hospitalization and treatment.”