The first gene of its kind identified in an outbred population, the gene linked to asthma susceptibility is known as ADAM33. ADAM33, a member of the protease sub-family known as metalloproteases, was identified through genetic screening of a large number of families from the United States and the United Kingdom. As part of an alliance with Schering-Plough, a leader in respiratory care, to develop therapies for asthma, researchers at Genome Therapeutics and University of Southampton amassed clinical information and biological samples from over 450 families that suffered from the disease. Using the samples obtained, Genome Therapeutics employed its proprietary disease-specific gene identification platform to identify candidate genes linked to an increased likelihood of suffering from asthma.
"The airways in asthma patients undergo a number of changes such as thickening of the airway walls and subsequent narrowing of the airway passage," stated Stephen Holgate, M.D., Medical Research Council Professor at the School of Medicine, University of Southampton, a lead collaborator on the project. "These changes contribute to the overall airway responsiveness and related breathing problems in asthma. Our studies suggest ADAM33 plays a role in this remodeling and may underlie abnormalities in asthmatic airway function."
"The ultimate goal of this alliance is the development of new therapeutics for the treatment and prevention of asthma. This research has provided not only a novel target for drug discovery, but also insights into the pathways and pathogenic mechanisms underlying asthma," said Cecil B. Pickett, Ph.D., President, Schering-Plough Research Institute. "Our successful collaboration with University of Southampton and Genome Therapeutics continues to provide unique opportunities in our asthma and allergy drug discovery programs," he said.
"This publication represents the culmination of a multi-year collaboration with our pharmaceutical partner Schering-Plough, which brought together University of Southampton's respiratory medicine expertise and Genome Therapeutics' capabilities in analyzing the genetics of complex human diseases," said Steven M. Rauscher, CEO and President of Genome Therapeutics. "Schering-Plough is well positioned to advance this discovery through drug discovery and development."
Research findings
In the paper, researchers detail the genetic approach and statistical analyses employed to determine the location and identification of genes linked to asthma in the patient population. Families with at least two children suffering from asthma were enrolled in the study. The affected subjects were required to have a diagnosis of asthma from a physician and be prescribed an asthma medication in order to be eligible. Following a genome-wide linkage analysis, the researchers identified several chromosomal regions as the likely location of the asthma genes, including chromosome 20p13. Further association studies on genes present in this chromosomal region validated that specific mutations in the ADAM33 gene were related to asthma susceptibility.
Rather than the allergic and immunological components that contribute to asthma, these genetic analyses suggest that ADAM33 is involved in the generation of bronchial hyperresponsiveness (BHR). The association of this gene with BHR and possible links with airway remodeling offers new avenues of research into the underlying causes of asthma. Furthermore, discovery of susceptibility genes for asthma offers the possibility in the future of identifying those individuals who are predisposed to asthma and initiating therapy early to prevent or ameliorate the disease process before permanent changes occur.
Published in the July 10th on-line edition of the journal Nature, the paper is available today at [web link to be inserted when available]. Titled "Association of the ADAM33 Gene with Asthma and Bronchial Hyperresponsiveness," the paper's senior author is Tim P. Keith, with Paul Van Eerdewegh, Randall D. Little, Josée Dupuis and Richard G. DelMastro contributing equally as lead authors. While the senior author and all lead authors are from Genome Therapeutics, researchers from University of Southampton and Schering-Plough made significant contributions to the work presented in this paper.
About Asthma
Classified as a chronic disabling condition by the Centers for Disease Control, asthma affects an estimated 14.9 million people in the United States and is responsible for nearly 5,000 deaths, 10 million missed school days and 134 million days of restricted activity every year. Asthma is said to be responsible for almost a half million hospitalizations each year with an average stay costing an estimated $3,100; direct economic and health care costs associated with the disease are nearly $14.5 billion per year.
In the United Kingdom, an estimated 5.1 million - 1 in 8 children and 1 in 13 adults - are currently being treated for the disease. In addition, an estimated 8 million people have been diagnosed with asthma at some stage in their lives, representing one person for every seven in the United Kingdom. Responsible for 74,000 emergency hospital admissions each year, the National Health Service estimates that the cost of treating asthmatics is close to £850 million a year ($1.3 billion U.S.).
About Genome Therapeutics
Genome Therapeutics is a biopharmaceutical company focused on the discovery and development of pharmaceutical and diagnostics products. The Company's first product candidate, Ramoplanin, is in a Phase III clinical trial for the prevention of bloodstream infections caused by vancomycin-resistant enterococci (VRE). Genome Therapeutics' biopharmaceutical business includes six major product discovery alliances with several pharmaceutical companies including
Schering-Plough, AstraZeneca, Wyeth and bioMérieux. In addition, Genome Therapeutics is involved in a joint venture with ArQule and possesses a significant portfolio of internal drug discovery programs. The Company's genomics services business, GenomeVision™ Services, provides pharmaceutical and biotechnology companies, and government and academic institutions with custom high-throughput sequencing, library construction, integrated SNP services and the PathoGenome™ Database.
About University of Southampton
The University of Southampton has an outstanding record of success in the provision of high-quality teaching across the range of university subjects, and is widely recognised for its leading-edge research and scholarship, its commitment to innovation in teaching and learning, and its support for business and industry through consultancy, research partnerships and technology transfer. For 15 years the medical school has had an internationally renowned respiratory research group whose work on asthma has been supported by the Medical Research Council.
About Schering-Plough
Schering-Plough is a research-based company engaged in the discovery, development, manufacturing and marketing of pharmaceutical products worldwide.
Forward-Looking Statement for Genome Therapeutics
This news release may contain forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements represent our management's judgment regarding future events. Forward-looking statements typically are identified by use of terms such as "may," "will," "should," "plan," "expect," "intend," "anticipate," "estimate," and similar words, although some forward-looking statements are expressed differently. We do not plan to update these forward-looking statements. You should be aware that our actual results could differ materially from those contained in the forward looking statements due to a number of risks affecting our business, including our inability to obtain, or delays in obtaining, the regulatory approvals necessary to commercialize our lead candidate, Ramoplanin, or our inability or the inability of our alliance partners to (i) successfully develop products based on our genomics information, (ii) obtain the necessary regulatory approvals, (iii) effectively commercialize any products developed before our competitors are able to commercialize competing products or (iv) obtain and enforce intellectual property rights, as well as the risk factors set forth in the Exhibit 99.1 to the Company's Annual Report on Form 10-K for the year ended December 31, 2001 and those set forth in other filings that we may make with the Securities and Exchange commission from time to time.
Journal
Nature