A therapy that is likely to make heart bypass surgery seem "incredibly primitive and even grotesque" within a decade was described to Cornell undergraduates April 25 by Todd K. Rosengart, head of cardiothoracic surgery at Evanston Northwestern Healthcare.
Speaking at the 16th annual Cornell Undergraduate Research Forum (CURB) in Schwarz Auditorium of Rockefeller Hall, Rosengart described how angiogenic gene therapy already has been used to grow new blood vessels in the hearts of 31 patients with coronary disease. "Gene therapy sounds very mysterious, but it is really nothing more than a drug-delivery strategy," said Rosengart, who previously was associate professor of cardiothoracic surgery at Weill Cornell Medical College and associate attending cardiothoracic surgeon at New York Presbyterian Hospital.
His talk was the focus of daylong oral and poster presentations of research and independent projects by nearly 60 Cornell undergraduates in philosophy, psychology, electrical engineering, chemical engineering, genetics, anthropology, sociology, chemistry and ecology. CURB is the only student-run organization of its kind in the nation.
This was the first year that the event had not been coordinated by Marilyn Williams, the assistant dean in the College of Arts and Sciences who retired last year. To celebrate Williams' tireless efforts at bringing the forum to national recognition, the Marilyn Emmons Williams Award will be given annually to a person who has been influential in furthering undergraduate research at Cornell. This year's award was presented to Bruce Monger, a senior research associate in the Department of Earth and Atmospheric Sciences. Presenting the award, John Silcox, vice provost for physical sciences and engineering, described Monger as "someone who is concerned with mentoring in the true spirit of the word -- helping people develop their own ideas."
Rosengart's work began in the mid-1980s with the study of vascular endothelial growth factor (VEGF), proteins that hold the promise of replacing surgery by enabling patients to grow their own vascular bypasses. "These are very, very potent and cause blood vessels to grow robustly. They are highly specific and only cause new blood vessels to grow and don't cause scars to grow in the heart," Rosengart said. His research team has found that injecting directly into the heart muscle is the most effective way of getting VEGF into the heart.
But the problem, they quickly found, is that VEGF on its own stays in the heart for too short a time. They turned to Ronald Crystal, professor of medicine at Weill Cornell Medical College and one of the world's leading authorities on using genes as drugs. Four years ago, the two groups combined their laboratories and began researching gene therapy for therapeutic angiogenesis, or the growth of new blood vessels.
The groups were able to use Crystal's pioneering work in using viruses widespread in nature, called adenoviruses, as a means of introducing growth factor into tissue. "The concept is to get VEGF into the heart muscle for a period of about a week," said Rosengart. "Less is not long enough, and longer can result in blood vessel tumors. By luck, the adenovirus lasts for about a week before the immune system wipes out its effectiveness."
Sections of the genome of the adenovirus type 5 -- which causes the common cold -- were removed to make the virus sterile. This was then coupled with VEGF genes and injected into the heart at the exact site where the growth of blood vessels was needed. "The genomes we put in is the software that we have temporarily wired to the cell. These are the instructions telling the cell which protein we want the cell to make. That is VEGF, and this heart muscle cell becomes a mini-factory producing the VEGF for about a week."
The patients who have been treated with this therapy since December 1997 showed marked improvement within six months to a year and have shown no signs of toxicity, he said. Furthermore, the heart does not have to be opened up but the virus can be injected through tiny incisions. There is even the hope that the treatment could become an outpatient procedure.
"Our hope is that within the next five years we will have approval from the FDA [Food and Drug Administration] for angiogenic gene therapy as the treatment of patients with coronary disease," Rosengart said. "There are tremendous opportunities in terms of what is going on and what will be possible in the next few years in the biological treatment for heart disease."
The CURB student presenters were Gabriel Benel, Jeffrey Biser, David Britton, Melissa Brooks, Keith Carter, Alessandro Cerruti, Shaun Chandran, Ruth Chen, Paul Chin, John Connelly, Nicole D'Amato, Jacque Darrell, Nate Eisinger, Lauren Feldman, Dorothy Fibiger, Laurel Freas, Amy Gershkoff, Evan Grant, Angela Gutierrez, Craig Halbmaier, David Ishikawa, Andrea Jackson, Karen Joslin, Jeremy Kipling, Christopher Konnor, Ben Leonard, Justin Lewis, Lisa Liu, Janelle Luk, Jean-Philip Lumb, Elidor Mehilli, Mena Mesiha, Michael Muccio, Anirban Mukherjee, Srihari Namperumal, Lauren Nicholas, Sylvia Odorcic, Jeonghoon Oh, Sonya Padron, Yvonne Pang, Kendyl Paulus, Laura Petes, Justin Portnoy, Ashutosh Sahu, D.M. Samuelson, Michael Schwaiger, Rebecca Scott, Stephen Shapiro, Ekundayo Spencer, Kiranmayi Sunkavalli, Chin Leong Teo, Eng Beng Toh, Elizabeth Vassallo, Raina White, Andrew Yee, Eugene Yeh, Katy Yu and Yiwen Zhang.
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