Tuesday February 1, 8:00 am Eastern Time
Company Press Release
SOURCE: Millennium Pharmaceuticals, Inc.
Millennium Identifies Role of Madh6 Gene and Smad6
Protein In Cardiovascular Defects
Tissue-Specific Role of Protein in Mice Could Serve as Model For Development of New Therapies
for Humans
CAMBRIDGE, Mass., Feb. 1 /PRNewswire/ -- Millennium Pharmaceuticals, Inc. (Nasdaq: MLNM - news) 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;
Millennium's 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.
SOURCE: Millennium Pharmaceuticals, Inc. |
