May 6, 2002
Cystic Fibrosis Foundation explores new research avenue with proteomics at The Hospital for Sick Children, Toronto
Cystic Fibrosis Foundation Therapeutics, Inc. (CFFTI), the drug discovery and development arm of the Cystic Fibrosis Foundation today announced that it has awarded $1,115,000 US to scientists at The Hospital for Sick Children and Affinium™ Pharmaceuticals, in Toronto, to harness the power of proteomics in the search for new cystic fibrosis (CF) therapies.
CF researchers are poised to explore proteomics, an innovative area of biomedical science, to discover potential therapeutics for CF and to form new diagnostic tools. Genomics, which is the technology used to identify genes, has furnished genetic "maps" for organisms from bacteria to humans These genes, in turn, produce proteins that serve as the cell's machinery. Scientists are using proteomics technology to identify all of the proteins in a cell or tissue, and to study protein functions and the interactions among these proteins. Proteins create and direct cellular functions, and abnormal protein interactions have been associated with disease, including CF.
Recently, automation of established methods to analyze proteins has made the technology more rapid and comprehensive. Recognizing this evolution in proteomics technology, the CF Foundation decided the time was right to make use of this powerful biomedical research strategy in CF.
"By supporting proteomics, the CF Foundation opens a brand new door in our search for a cure or control for CF," said Robert J. Beall, Ph.D., president and chief executive officer of the CF Foundation and CFFTI. "We are particularly hopeful about the potential of proteomics because it offers the possibility of discovering drug targets to correct the root cause of the disease."
Seeing the huge drug discovery potential of this field for CF research, CFFTI gave a proteomics research award to Gergely L. Lukacs, M.D., Ph.D., senior scientist at The Hospital for Sick Children Research Institute and associate professor of laboratory medicine and pathobiology at the University of Toronto.
For more than eight years, Lukacs and colleagues have been investigating how the CF gene's protein product - Cystic Fibrosis Transmembrane conductance Regulator (CFTR) - moves through certain cells. They have developed tissue culture models and biochemical assays that allow them to follow the fate of normal and mutant CFTR protein.
Normally, the CFTR protein is found in cells that line certain organs, including the lungs and the pancreas. CFTR's function is to form a channel for the flow of chloride particles through the cell membrane. In CF, the mutant protein fails to perform its job - either not at all or insufficiently - leading to an imbalance of salt and water at the inner lining of these organs. Abnormally thick, sticky mucus develops, causing the progressive respiratory and digestive problems that characterize CF.
During its lifespan, CFTR interacts with at least a few dozen other proteins in the cell - only a small fraction of the proteins have been identified, explained Lukacs. Some of these "protein partners" of CFTR may be involved in retaining mutant CFTR inside the cell, rather than allowing it to gather at the cell surface to act as a functioning chloride channel.
"Identifying the interacting proteins would help us to understand the physiological function and regulation of CFTR in the healthy cell environment, and provide future drug targets if these interactions are impaired or missing in CF cells," said Lukacs. "The long-term goal of our project is to identify drugs to alleviate the clinical symptoms of patients with CF."
The Hospital for Sick Children has an exceptional track record on CF basic and clinical research accomplishments, including co-discovering the gene that causes CF in 1989. The CF-specialized patient care center here established a large CF clinical database of patients in Canada, starting in the late 1970s, which continues to be an invaluable resource. In addition, the CF Genetic Consortium Database, supervised by Lap-Chee Tsui, Ph.D., contains more than 1,000 CF-associated gene mutations.
Lukacs collaborates with scientists from Affinium Pharmaceuticals, Toronto, on this project. Founded as Integrative Proteomics, Inc., Affinium Pharmaceuticals is a structure-guided drug discovery company. Affinium's proprietary, integrated drug discovery process is designed for rapid advancement of small molecule programs from gene to clinic. Affinium's processes enable high-throughput target production, and determination of target function and structure.
Another use of proteomics in this new CF Foundation-funded research strategy involves identifying proteins that could function as "biomarkers" of the disease's status, such as a patient's degree of lung damage or response to treatment.
The Cystic Fibrosis Foundation was created in 1955 to assure the development of the means to cure and control CF and to improve the quality of life for people with the disease. The CF Foundation's proteomics research initiative is part of its innovative Therapeutics Development Program, which supports the full spectrum of CF drug development from discovery to clinical evaluation. Matching milestone-driven awards to support CF drug discovery and development are offered to biotechnology companies and academic institutions through this program. Promising new drugs are then streamlined through clinical trial evaluations in the CF Foundation's network of specialized care centers.
CFFTI is a nonprofit affiliate of the CF Foundation that operates drug discovery, development and evaluation efforts. CFFTI is made up of industry and academic researchers and members of the CF Foundation Board of Trustees. Total support of CFFTI is provided by the CF Foundation. For more information on the CF Foundation and CFFTI, please visit www.cff.org.
Contact:
Allison M. Tobin
Director of Media Relations
Cystic Fibrosis Foundation
(301) 841-2665
Laura Greer
Manager, Public Affairs
The Hospital for Sick Children
(416) 813-5046
Public Affairs
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