Cellular and genetic therapies may hold the key to better outcomes for patients suffering from critical limb ischemia, a condition in which a serious obstruction of the arteries reduces blood flow to the feet, legs or hands, according to Omaida C. Velazquez, M.D., the David Kimmelman Endowed Chair in Vascular and Endovascular Surgery at the University of Miami Miller School of Medicine.
“A patient’s bone marrow-derived cells, bone marrow stem cells from donors, and gene therapy using an adeno-associated virus as a carrier are promising approaches,” said Dr. Velazquez, professor and chair of the DeWitt Daughtry Family Department of Surgery and surgeon-in-chief at UHealth – the University of Miami Health System, and Jackson Health System.
Dr. Velazquez gave the 30th annual Conrad Jobst Lecture on November 8 to more than 200 physicians and researchers from throughout the U.S. The lecture was hosted by the University of Michigan Department of Surgery’s Section of Vascular Surgery, in Ann Arbor, and co-sponsored by The Jobst Vascular Institute, which is based in Toledo, Ohio.
In her talk, Dr. Velazquez highlighted recent developments in the treatment of peripheral artery disease (PAD) and clinical limb ischemia (CLI), including her collaborative research at the Miller School’s Vascular Laboratory with Zhao-Jun Liu, M.D., Ph.D., research associate professor. “We are developing a new gene-modified cell-based therapy and a direct gene therapy to help regenerate the blood vessels and reprofuse the compromised tissues,” she said. “These new treatments are now being patented by the University of Miami, and we recently signed a licensing agreement to develop this technology further.”
Dr. Velazquez said standard treatments for CLI, including medications, surgical bypass or angioplasty/stent procedures, are not effective in a high percentage of patients. As a result, limb amputation is necessary in about 130,000 U.S. patients a year.
Other ways to restore the flow of blood include the use of transplanted bone marrow stem cells from the patient or from young bone marrow donors. This vascular regeneration strategy can improve wound healing, reduce pain and improve amputation-free outcomes, she said. However, not every patient responds to this therapy, particularly since cell products vary from person to person.
Another approach is the AAV delivery of the E-selectin gene via a single-dose intramuscular injection to the affected limb or the transplantation of “supercharged stem cells” that have been activated by a similar gene therapy strategy. This can improve reverse healing deficits, and lead to tissue regeneration in patients with and without diabetes, she said.
Dr. Velazquez’s research focuses on further understanding and advancing new treatments for lower extremity arterial occlusive disease and diabetes-related wound healing defects. She and Dr. Liu are the co-principal investigators of a National Institutes of Health-funded science laboratory that investigates endothelial cell biology, angiogenesis, and vasculogenesis. Seminal findings from their research have paved the way to novel cell-based and gene therapy clinical trials for PAD, CLI, and diabetic non-healing wounds. This technology also has the promise of serving as a platform for coronary artery disease and other types of regenerative medicine applications.
Noting that Conrad Jobst patented and developed the Jobst elastic stockings for venous insufficiency in the 1940s, Dr. Velazquez said, “He was an engineer, an entrepreneur, and a great innovator who saw an unmet medical need and set out to address it. It is a powerful example of how the convergence of principles from many different fields can be a great catalyst for innovation in vascular disease, academic surgery, and throughout medicine and health care.”
Jobst’s wife Caroline endowed the Jobst Lecture series beginning in 1990. Prior presenters included the late James A. DeWeese, M.D., a pioneer in cardiothoracic and vascular surgery at the University of Rochester; Russell Ross, M.D., whose work at the University of Washington contributed to the understanding of atherosclerosis; and Robert B. Rutherford, M.D., a professor at the University of Colorado who helped develop uniform standards for reporting vascular practices in professional literature.