For Immediate Release -- December 17, 1996
Media Contact: Cheryl Greenhouse 617-252-7785
Genzyme Announces Cardiovascular Gene Therapy Program
CAMBRIDGE, Mass. -- Genzyme Corp.'s General Division announced today that it has commenced a gene therapy program that will concentrate on the development of molecular therapies to treat cardiovascular disease.
As an initial focus, the company will be working with scientists at Duke University and the University of California, San Diego (UCSD), to develop treatments for congestive heart failure, vein graft failure, and restenosis. Additionally, through its collaboration with UCSD, Genzyme will be developing a gene therapy application to protect heart tissue from oxygen damage that can occur during various types of cardiac procedures.
Both collaborations call for Genzyme to provide vectors to support pre-clinical research and future clinical trials in exchange for rights to any products resulting from the collaboration.
"Cardiovascular disease is the leading cause of death in the United States, and we are pleased to be expanding our gene therapy research into this important area," said Gail Maderis, Genzyme's vice president for gene therapy. "We look forward to combining the cardiovascular expertise of researchers at Duke and UCSD with Genzyme's gene delivery capabilities to develop innovative approaches for treating this disease area."
In the Duke collaboration, Genzyme will provide adenoviral and cationic lipid-based vectors to Walter J. Koch, Ph.D., and Robert J. Lefkowitz, M.D., who will use the vectors with proprietary technology they have developed for treating congestive heart failure, vein graft failure, and restenosis.
In congestive heart failure, the heart loses its ability to be stimulated by the body's natural stimulants and by drugs such as epinephrine. There are two approaches which are being investigated. The first is to increase the number of receptors for epinephrine through the use of beta-adrenergic receptor genes. Expression of this gene is reduced in chronic congestive heart failure. Studies in transgenic animals have demonstrated that increased expression of the beta-adrenergic receptor gene can lead to marked improvement in the heart's ability to function.
The second approach is to prevent the desensitization of that receptor with a novel gene construct, the beta-adrenergic receptor kinase inhibitor. Koch and Lefkowitz hope to restore the heart's ability to be stimulated by natural means by using Genzyme's vectors to transport these genes to cardiac muscle cells.
The beta-adrenergic receptor kinase inhibitor gene also may be useful in the treatment of vein graft failure and restenosis because it has been shown to interfere with growth factor signaling pathways. Surgical techniques that clear a patient's arteries of blockages cause damage to the arterial wall. This can result in the release of growth factors which stimulate cell growth to repair the damaged area. Often, however, the growth factor signal stimulates an inappropriate type of cell to grow. Instead of repairing the damage with arterial wall and ephelial cells, vascular smooth muscle cells begin filling the damaged portions of the artery, leading to another blockage or restenosis.
This unchecked vascular smooth muscle growth also occurs in vein grafts used in cardiovascular surgery. Drs. Koch and Lefkowitz will apply the beta-adrenergic receptor kinase inhibitor gene to vein grafts prior to surgical implantation in attempts to decrease the incidence of vein graft closure which currently is a major problem.
In its collaboration with UCSD, Genzyme will work with Wolfgang Dillmann, M.D., on two different technologies. First, the use of heat shock protein 70 will be explored as a protective mechanism against heart tissue damage that can occur during injuries associated with the loss of blood flow to the heart. Over-expression of the protein has been shown to reduce the size of experimentally-induced tissue death by 40 percent. Dillmann and his associates have demonstrated this protective effect in transgenic mice [Journal of Clinical Investigation, 95 (4), 1446-1456, 1995].
The second technology involves the use of the sarcoplasmic reticulum calcium ATPase (SERCA-2) in congestive heart failure. SERCA-2 is associated with increased flow of calcium across cell membranes. One of the signs of congestive heart failure is a weak heartbeat. The strength of the heartbeat is regulated in part by the flow of calcium across the cell membrane. By expressing SERCA-2 within the heart tissue, it may be possible to increase the calcium flow and strengthen the heartbeat.
Genzyme has developed viral and lipid-based vector systems to support the commercialization of gene therapies. The company is focusing on applications for genetic disease, cancer, cardiovascular therapy, and infectious disease. With fully integrated capabilities, Genzyme has participated in nine clinical studies in gene therapy to date at eight clinical sites in the U.S. and Europe, and established productive collaborations with leading academic groups.
Genzyme continues to look for additional collaborations in cardiovascular gene therapy as it expands its program, and is actively seeking corporate partners with an interest in the cardiovascular market to commercialize these technologies.
One of the world's top five biotechnology companies, Genzyme focuses on developing innovative products and services for major unmet medical needs. The company's General Division develops and markets pharmaceuticals, genetic diagnostic services, and diagnostic, surgical, and specialty therapeutic products.
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