Gene therapy efficacy trial begins at St. Michael’s Hospital

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St. Michael’s Hospital/University of Toronto researchers recently announced the NORTHERN trial – [NJC1]North America’s first multi-centre efficacy trial using catheter injection of genes into the heart muscle for the treatment of cardiovascular disease. On August 28, 2002, researchers injected the first patient with a DNA treatment (vascular endothelial growth factor) or matching placebo using the NOGA mapping system. While previous studies examined the safety of gene therapy, this research study has been designed to determine its effectiveness for patients who have few other treatment options.

The NORTHERN (NOGA Angiogenesis Revascularization Therapy: Evaluation by RadioNuclide Imaging) study is a randomized, double-blind, placebo-controlled, non-surgical, cardiac gene therapy trial. Approximately 110 patients who have stable and severe angina, but are not able to have other forms of treatment, will be recruited for the study. “About 15 per cent of patients with very symptomatic coronary disease cannot undergo the traditional bypass procedure and are not suitable for angioplasty, the opening of blocked arteries using a balloon,” says Dr. Duncan Stewart, lead investigator and head, Division of Cardiology, St. Michael’s Hospital; director, Division of Cardiology and professor of medicine, University of Toronto. “These patients have had previous medical treatment which has failed and they continue to have debilitating angina (chest discomfort) which affects their quality of life.”

A navigational catheter is used to create a three-dimensional map of the heart and reveals which areas have poor blood supply. Once the heart is mapped, a placebo or gene therapy is injected into these specific areas using the catheter. It is hoped that the gene therapy injections will stimulate the development of new arteries in the patient’s heart muscle. “The NOGA mapping system is an exciting new technology which allows us to identify and target places in the heart which are not receiving adequate amounts of blood,” says Dr. Michael Kutryk, clinician scientist and interventional cardiologist, St. Michael’s Hospital; and assistant professor of medicine, University of Toronto. “These are areas which cannot be bypassed and should most benefit from the growth of new arteries.”

The NORTHERN trial has been designed to gather objective data which will determine if the injection of genes into the heart muscle using a catheter is a potentially effective new treatment for heart disease. “Using a catheter allows delivery of the growth factors without the need for surgery and permits proper blinding which ensures valid study results,” says Stewart.

“This is a landmark study that uses a combination of innovative technology and gene therapy, which promises to be the future of therapeutic medicine,” says Kutryk.

“St. Michael’s Hospital is uniquely positioned to perform such a trial because of its strong basic science and research departments as well as a dedicated clinical team. This is a major advancement in gene therapy research.”

For patients who have been told there are no other options to treat their heart disease, this study offers hope. “It is very depressing to not be able to do things like lift my grandchildren without experiencing chest pain,” says Terence Deane, the first patient to participate in the clinical study. “At least now I have a little hope that my symptoms might improve and maybe I’ll even get to see my grandchildren grow up.”

The Northern Trial will be conducted at six other cardiac centres across Canada including Mount Sinai Hospital, Montreal Heart Institute, Laval Hospital, Victoria Heart Institute, Sunnybrook and Women’s College Health Science Centre, and the University of Alberta Hospital. Grant funding for the study has been obtained from Cordis/Biosense Webster (a Johnson and Johnson company), the Canadian Institutes for Health Research (CIHR), Heart and Stroke Richard Lewar Centre of Excellence (HSRLCE), the Canadian Foundation for Innovation (CFI), the Heart and Stroke Foundation of Ontario (HSFO) and St. Michael’s Hospital Foundation.

St. Michael’s Hospital is a Catholic research and teaching hospital, fully affiliated with the University of Toronto, specializing in heart and vascular disease, diabetes comprehensive care, inner city health, trauma and neurosurgery, minimal access therapeutics, and neurological and musculoskeletal disorders.