Researchers at ZymoGenetics, Inc. announced today the discovery of a potential new therapy for lupus, and possibly other autoimmune diseases . Administration of a novel immunosuppressive agent developed at ZymoGenetics inhibited disease symptoms and prolonged life in a mouse model of systemic lupus erythematosus (SLE). This research, reported in the April 27, 2000 issue of Nature, demonstrates the important role genomics can play in the discovery of novel pharmaceuticals.
Researchers hope that this discovery could lead to breakthrough treatments for a variety of immunological diseases, such as lupus, myasthenia gravis, rheumatoid arthritis, multiple sclerosis, psoriasis, and perhaps certain types of lymphatic cancers.
"We were one of the first to recognize the powerful opportunity to identify protein therapeutics from genomics approaches," said ZymoGenetics President and CEO, Bruce L.A. Carter, Ph.D. "Our discovery that the soluble TACI receptor inhibits symptoms of autoimmune disease provides further validation of our strategy, which combines expertise in genomics and biology to turn novel proteins into therapeutic candidates."
How the New Treatment Worked in Mice B cells play an important role in the body's immune system by producing antibodies, which attach to foreign matter and initiate a normal immune response.
In diseases of autoimmunity like lupus, B cells go awry and produce antibodies that attack the body in a destructive manner. In SLE patients, the amounts of these circulating antibodies become too great for the body to effectively eliminate, eventually resulting in kidney damage and sometimes death.
The immunosuppressive agent under investigation at ZymoGenetics, termed soluble "TACI," is a modified form of a receptor that is found on the surface of B cells. Soluble TACI works by capturing a cytokine in the blood that stimulates B cells to make antibodies. In diseased mice treated with soluble TACI, this captured cytokine was unable to act on B cells. The proportion of B cells decreased, and these mice lived longer and had less severe disease symptoms. Researchers are continuing to investigate the use of soluble TACI to regulate B cell activities, including the inhibition of production of destructive antibodies against the body.
"We have established an important relationship between TACI and SLE in mice," said lead author on the Nature paper, Dr. Jane Gross. "We can now examine the utility of the soluble TACI receptor as a therapeutic for other autoimmune diseases."
The unmodified TACI receptor was discovered separately by ZymoGenetics and St. Jude Children's Research Hospital. ZymoGenetics has taken an exclusive license to intellectual property owned by St. Jude Children's Research Hospital relating to the unmodified receptor.
Background on Lupus
Over one million people in the United States suffer from SLE, and of these, an estimated 200,000 have sustained severe organ damage, requiring them to take immunosuppressive drugs to help them control the disease. Many of these drugs have debilitating side effects, so there is a clear need for treatments that act more specifically. There have been no fundamental advances in the treatment of SLE since the 1970s. In addition to SLE, more than fifty diseases are thought to involve autoimmunity. Researchers at ZymoGenetics are hopeful that soluble TACI will ultimately prove successful in the treatment of autoimmune diseases.
ZymoGenetics, founded in 1981, currently leverages its expertise in bioinformatics and biology to discover and develop novel therapeutic proteins. Several product candidates that address significant disease markets are in preclinical development under a strong patent portfolio. ZymoGenetics' successful track record of protein discovery and genetic engineering places it among the top biotech companies in terms of the number of marketed products derived from its work. These include:
- human insulin (Novolin®) marketed for insulin dependent diabetics by Novo Nordisk A/S
- Factor VIIa (NovoSeven® Coagulation Factor VIIa Recombinant), also marketed by Novo Nordisk A/S, for the treatment of bleeding episodes in hemophilia A or B patients with inhibitors
- platelet-derived growth factor (becaplermin) for treating non-healing diabetic ulcers
- analog of tissue plasminogen activator (monteplase), which is marketed in Japan for the treatment of myocardial infarction
- glucagon (GlucaGen® [glucagons (rDNA origin) for injection], approved for use as a diagnostic aid during radiological examinations and for the treatment of severe hypoglycemia in diabetic patients treated with insulin, which was outlicensed for US marketing to Bedford Laboratories
For further information please contact:
Charles E. Hart, Ph.D
Novo Nordisk A/S:
Susan Toth Jackson
Peter Lundby Hansen