Monday, June 15, 2015

Loyola Study Could Help Improve Gene Therapy for Heart Disease, Cancer

Research Also May Aid Fight against Tuberculosis, Malaria

MAYWOOD, Ill. -- A Loyola University Chicago Stritch School of Medicine study could lead to improved gene therapies for conditions such as heart disease and cancer as well as more effective vaccines for tuberculosis, malaria and other diseases.

Senior author Christopher Wiethoff, PhD, and colleagues report their findings in the October issue of the Journal of Virology. Editors spotlighted the report as one of the “articles of significant interest.” Journal of Virology is the leading journal of the study of viruses.

The study involved a virus that causes the common cold, called adenovirus. Scientists have been trying to use a version of this virus as a delivery vehicle for gene therapies and vaccines. (The virus is not able to reproduce and cause disease.) Administering this virus to patients causes an inflammatory reaction, which can be a double-edged sword: The reaction aids in the use of the virus in vaccines but limits its use for gene therapies.

In gene therapy, one or more desired genes are introduced into the adenovirus, which is then administered to the patient. Once in the body, the virus enters targeted cells and delivers the desired genes. In heart disease patients, for example, the virus delivers genes that trigger the growth of new blood vessels in damaged heart muscle. However, when the adenovirus enters a cell to deliver a desired gene, it causes an inflammatory immune response. In extreme cases, this can endanger the patient. In one highly publicized case, a University of Pennsylvania gene therapy patient named Jesse Gelsinger died from a massive immune response triggered by the use of the adenovirus.

In vaccines, the adenovirus delivers one or more genes. These genes instruct cells to produce a specific protein, which is normally part of the targeted pathogen. This protein, in turn, jump-starts the patient’s immune system to attack a specific pathogen, such as the bacterium that causes tuberculosis or the parasite that causes malaria. Here, the inflammatory immune response has the beneficial effect of revving up the immune system to attack germs.

The Loyola study provides new insights into how the adenovirus triggers an immune response. The study involved immune cells from humans and mice. Researchers discovered how cells sense the adenovirus as it enters a cell. This recognition, in turn, triggers the immune response.  The finding could help researchers tailor the adenovirus so that it causes less of an immune response in gene therapy applications and an enhanced immune response in vaccines.

“These results will help with future studies of innate immune responses to adenovirus,” Wiethoff and colleagues wrote. “Additionally, our understanding of this process could allow us to either enhance or attenuate [weaken] the innate immune response to adenovirus to generate novel vectors for gene therapy and vaccination."

Wiethoff is an assistant professor in the Department of Microbiology and Immunology at Loyola University Chicago Stritch School of Medicine. Other authors, all in the Department of Microbiology and Immunology, are Kathleen McGuire (first author), Arlene Barlan and Tina Griffin.

Wiethoff and McGuire have received funding from the National Institutes of Health, and Wiethoff has received funding from the American Heart Association.

About Loyola University Health System

Loyola University Health System (LUHS) is part of Trinity Health. Based in the western suburbs of Chicago, LUHS is a quaternary care system with a 61-acre main medical center campus, the 36-acre Gottlieb Memorial Hospital campus and more than 30 primary and specialty care facilities in Cook, Will and DuPage counties. Loyola University Medical Center’s campus is conveniently located in Maywood, 13 miles west of Chicago’s Loop and 8 miles east of Oak Brook, Ill. At the heart of the medical center campus is a 559-licensed-bed hospital that houses a Level 1 Trauma Center, a Burn Center and the Ronald McDonald® Children's Hospital of Loyola University Medical Center. Also on campus are the Cardinal Bernardin Cancer Center, Loyola Outpatient Center, Center for Heart & Vascular Medicine and Loyola Oral Health Center as well as Loyola University Chicago Stritch School of Medicine, Loyola University Chicago Marcella Niehoff School of Nursing and the Loyola Center for Fitness. Loyola's Gottlieb campus in Melrose Park includes the 255-licensed-bed community hospital, the Professional Office Building housing 150 private practice clinics, the Adult Day Care, the Gottlieb Center for Fitness, Loyola Center for Metabolic Surgery and Bariatric Care and the Loyola Cancer Care & Research at the Marjorie G. Weinberg Cancer Center at Melrose Park.

Trinity Health is a national Catholic health system with an enduring legacy and a steadfast mission to be a transforming and healing presence within the communities we serve. Trinity is committed to being a people-centered health care system that enables better health, better care and lower costs. Trinity Health has 88 hospitals and hundreds of continuing care facilities, home care agencies and outpatient centers in 21 states and 119,000 employees.