Dr. Jeffrey M. Isner 1947–2001
Authors: Elizabeth G. Nabel
Journal: Molecular Therapy (2001)

We have lost a leader in cardiovascular gene therapy and therapeutic angiogenesis. Jeffrey M. Isner died on October 31, 2001, at his home in Weston, Massachusetts, at the age of 53. The cause was a heart attack. Jeff Isner was an interventional cardiologist who worked at St. Elizabeth's Hospital for two decades and was on the faculty of Tufts University. Jeff developed an early interest in the clinical syndrome of restenosis, the process by which a smooth muscle cell-rich lesion redevelops within the site of angioplasty dilatation 3 to 6 months after the initial procedure. When I met Jeff in 1989, he had spent several years exploring the role of intravascular laser devices to treat restenosis, but to no avail. He was firmly committed to alternative strategies to treat vascular diseases and quickly saw the promise of gene transfer. On numerous occasions, we discussed applications of gene transfer to blood vessel diseases and visited each other's laboratories, sharing methods and data from our respective vascular gene transfer studies. Jeff was firmly committed to developing the technology and to clinical applications. In the early 1990s, Jeff turned his attention to the burgeoning field of angiogenesis. He and others reasoned that vascular endothelial growth factor (VEGF) could induce new blood vessel growth in patients with peripheral vascular disease. After a series of proof-of-principle experiments in rabbits, Jeff put the idea to the test in 1994, being the first to coat angioplasty catheters with plasmid DNA encoding VEGF and to treat patients with peripheral vascular lesions. He coined the term “therapeutic angiogenesis,” and over the past 7 years he treated over 200 patients in various protocols for myocardial and peripheral angiogenesis. Many questions still need answers before gene therapy becomes standard treatment for vascular disease. Although his studies were promising, Jeff faced significant hurdles. A demonstration that intact collateral vessels—rather than leaky capillaries—were formed following treatment is lacking. Evidence that increased blood flow persisted for many months is not yet obtained. Jeff's early successes also placed him in the middle of the debate regarding the role of physicians conducting clinical studies sponsored by companies in which they had a financial interest. Last year, the Food and Drug Administration temporarily suspended the research conducted by Jeff, Vascular Genetics (a company he founded), and St. Elizabeth's, claiming that the researchers had failed to properly report the death of two patients participating in a study. Jeff said that the two patients had died of underlying cardiovascular disease, rather than the treatments. But the company acknowledged administrative problems with the research and corrected the situation. Jeff resumed his studies this past spring, and recently received a Center of Excellence in Gene Therapy grant from the National Heart, Lung, and Blood Institute. His patients gathered this summer at St. Elizabeth's to acknowledge his pioneering work and to encourage its continuation. Jeff was undaunted in spirit and vowed to continue his work. In addition to his clinical studies in angiogenesis, Jeff made other important scientific contributions. He was one of the first researchers to demonstrate the presence of endothelial cell progenitors in the bone marrow, and subsequent studies have established the role of endothelial cell progenitors in the process of angiogenesis. Jeff will be remembered as a courageous and committed physician. He cared deeply for his patients, and he was passionate in his desire to bring gene therapy to viable clinical treatments. The gene therapy and cardiovascular communities will miss his creativity and energy. Jeff was not only an innovator, he also inspired many trainees to pursue clinical research. It is tragic indeed that his life ended before he witnessed his and others’ research come to fruition—angiogenesis therapies on the market and routinely used to treat patients with atherosclerosis. This will be his legacy, and one that he would have thoroughly enjoyed.