Tissue-specific role of protein in mice could serve as model for development of new therapies for humans
CAMBRIDGE, Mass., February 1, 2000 -- Millennium Pharmaceuticals, Inc. (Nasdaq: MLNM) today announced the publication of data from its ongoing collaboration with Eli Lilly and Company in the area of cardiovascular disease. The study, which appears in the February 1, 2000 issue of Nature Genetics, demonstrates the tissue-specific role of the Smad6 protein in the cardiovascular system. Mice, in which the gene encoding the Smad6 protein is disrupted, have multiple cardiovascular abnormalities. These findings have significant potential for accelerating the development of therapies to treat a wide range of defects affecting the heart and blood vessels. Millennium and Brigham and Women's Hospital co-own U.S. Patent No. 5,834,248 which relates to the gene encoding the Smad6 protein.
The paper, titled "A Role for Smad6 in Development and Homeostasis of the Cardiovascular System," by Katherine Galvin, Ph.D. and colleagues at Millennium, the University of Cincinnati and Harvard University, describes how mutations in the Madh6 gene, which encodes the Smad6 protein, result in a variety of cardiovascular abnormalities in mice. Most significantly, the data shows that alterations in Madh6 gene expression and Smad6 protein function affect only the cardiovascular system. This suggests that the Madh6 gene and the Smad6 protein may have significant utility in developing novel therapies for cardiovascular disease.
Smad6 is a member of a family of proteins that help convert signals from outside the cell into changes in gene expression. The observed cardiovascular defects in mice with a disrupted Smad6 gene include abnormalities of the heart valves and blood vessels, hardening of the arteries and increased blood pressure. Similar hardening of the arteries occurs in humans as a clinically significant feature of atherosclerotic lesions.
"The determination that Madh6 gene expression is restricted to the cardiovascular system provides us with a key cardiovascular-specific target," said Dennis Huszar, Ph.D., director of target validation at Millennium. "This discovery gives us the potential to correct the underlying molecular abnormalities that lead to cardiovascular disease, rather than merely creating drugs to treat the symptoms."
"The discovery of Madh6 and the elucidation of its role in the cardiovascular system is indicative of our ability to identify disease-related genes and rapidly determine how they impact the initiation and progression of that disease," said Robert Tepper, M.D., chief scientific officer of Millennium. "Our integrated science and technology platform, which spans from gene-to- patient, combines the best technology with biological expertise. This enables Millennium to play a leading role in the discovery of novel disease targets for the development of potential therapeutics, especially in areas of unmet medical need."
Background
The American Heart Association reports that approximately 60 million Americans have one or more forms of cardiovascular disease (CVD) which includes stroke, hypertension, coronary heart disease and congestive heart failure. CVD is the single leading cause of death in America today. More than two million people in the United States suffer from the effects of congestive heart failure (CHF) and approximately 400,000 new cases are diagnosed each year. CHF results from altered cardiac muscle mechanics and function in response to various conditions including: hypertension, valvular heart disease, and heart attacks due to atherosclerosis. The response of the cardiac muscle to these conditions is felt to be largely under the genetic control of several, complex signaling pathways. Therefore, it is thought that by modulating novel molecular targets in the cardiovascular system, CHF and other forms of CVD may be more effectively treated.
In October 1995, Millennium and Lilly entered into a research agreement utilizing Millennium's gene discovery and target validation technology platform to identify targets for drug candidate screening in cardiovascular disease to Lilly. In September 1997, Millennium and Lilly extended the collaboration for three additional years. Under the terms of the agreement, Millennium shares with Lilly select proprietary genomics technologies and expertise, allowing Lilly to expand its in-house genomics programs. In exchange, Lilly shares with Millennium proprietary high throughput screening technologies and access to select combinatorial chemistry libraries of Sphinx Pharmaceuticals, a division of Lilly Research Laboratories. The two companies also have an agreement in select fields of oncology.
Millennium, a leading drug discovery and development company, employs large-scale genetics, genomics, high throughput screening and informatics in an integrated science and technology platform. The Company is applying this platform to integrate the initial discovery of disease-related genes, the development of drugs specific for these diseases and the management of patients affected by these diseases. Headquartered in Cambridge, Massachusetts, Millennium and its affiliates currently employ more than 1,000 people.
This press release contains forward-looking statements that involve a number of risks and uncertainties. Among the factors that could cause actual results to differ materially from those indicated in such forward looking statements include uncertainties relating unanticipated difficulties and delays relating to gene identification, drug discovery and clinical development processes; Millennium¹s ability to successfully integrate the operations of LeukoSite, Inc.; changes in relationships with strategic partners and dependence upon strategic partners for the performance of critical activities under collaborative agreements; the impact of competitive products and technological changes; uncertainties relating to patent protection and regulatory approval; and uncertainties relating to the ability of Millennium and its affiliates to obtain substantial additional funds required for progress in drug discovery and development. The factors that could affect the performance of Millennium are more fully described in filings by Millennium with the Securities and Exchange Commission including but not limited to the factors set forth under the heading "Risk Factors" in the registration statement on Form S-4 filed by Millennium with the Securities and Exchange Commission on November 5, 1999.
Editor's Note: This release is available on Millennium's home page at www.mlnm.com.
Other Contacts:
Clare Midgley (investor)
Sally McCraven (media)
Millennium Pharmaceuticals, Inc.
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Journal
Nature Genetics