CAMBRIDGE, SANTA CLARA, SEATTLE — Aug. 6, 2002 — The Hereditary Disease Array Group (HDAG) today reported important new findings on Huntington's disease, in six peer-reviewed papers published in the online version of the August 15th issue of Human Molecular Genetics. The papers are part of the HDAG's two-year research effort that brought over 50 scientists from 19 universities together to discover how the mutant Huntington's disease gene causes brain cells to die by affecting other biological pathways.
The HDAG used Affymetrix GeneChip microarrays to conduct whole-genome analysis on a variety of different disease models. Those data were then compiled in the HDAG NeuMetrix gene expression database, which was custom-built by 3rd Millennium to analyze the results and is free and publicly available to all researchers at www.neumetrix.info. This worldwide collaborative research effort has advanced new strategies for treating Huntington's disease and related disorders that involve brain degeneration.
"The team effort from the Hereditary Disease Array Group represents a glimpse of a scientific utopia," said Nancy Wexler, Hereditary Disease Foundation (HDF) President. "This is what is possible when everyone collaborates to do what is best for patients."
Huntington's disease is a neurodegenerative disorder that causes progressive deterioration of cognitive processes and memory as well as the gradual development of involuntary movements in all parts of the body. Since the Huntington's disease gene was discovered in 1993, scientists have sought to understand how resultant changes in the protein, "huntingtin," causes neurodegeneration. Researchers have generated powerful models of the disease in mice, yeast, fruit flies and isolated brain cells by introducing the mutant form of the gene.
Two years ago many of these researchers joined forces and, in a collaborative effort organized by the Hereditary Disease Foundation, created the HDAG. The group's goal was to create an expression database which they hoped would reveal the biological pathways affected by the mutant Huntington's disease gene. To speed research and get the most comparable results possible, the HDAG scientists standardized their experimental methods using a single, robust microarray platform and consistent sample preparation methods.
"Had we done these experiments independently, it would have taken a decade to sort out the findings," said Jim Olson M.D., Ph.D., Assistant Member of the Fred Hutchinson Cancer Research Center and coordinator of the HDAG. "By cooperating, working on a standardized technology platform and sharing data from day one, we were able to complete the studies in a rapid time frame."
Each paper reports a different aspect of the group's important discoveries, including:
1) The identification of the group of genes first altered by the mutant Huntington's disease gene, which may lead to new therapies that are focused on the earliest stages of disease progression;
2) The finding that genetic changes in muscle tissue mirror those in the brain in patients with Huntington's disease. In the future, the progression and treatment of Huntington's disease may be monitored by studying muscle tissue rather than accessing the brain;
3) The finding that many of the changes that occur in the Huntington's disease model also occur in models of other degenerative brain disorders, suggesting common pathways that might be targets for new therapies;
4) The Huntington's disease protein causes many more gene-level changes when it is cleaved, or broken down, which occurs as people age, than when it is complete. This finding supports further research on therapies that prevent protein breakdown.
A number of studies based on the HDAG findings are underway to test potential drugs that may prevent the mutant disease protein from altering the expression levels of other critical genes. Pre-clinical studies are now being conducted in the same models that were used in the HDAG research with the hope that some of the drugs will reach human clinical trials within the next five years, said Olson. The studies were funded primarily by the Hereditary Disease Foundation and the National Institutes of Health.
"From a research standpoint, the HDAG's progress is a model for how scientific collaborations can perform beautifully," said Richard Dweck, CEO of 3rd Millennium. "We applaud the HDAG's approach and their ability to integrate both the research and the researchers. 3rd Millennium developed the NeuMetrix Database to improve data management and interpretation, previously a major bottleneck for the HDAG, and we are delighted that the benefits of the NeuMetrix database will soon be available to the general public."
"Affymetrix will continue to support collaborative research efforts that propel our understanding of devastating conditions like Huntington's disease forward," said Stephen P.A. Fodor, Ph.D, Affymetrix Founder and Chief Executive Officer. "The group's findings clearly demonstrate the power of gene expression monitoring for revealing the cascade of biological changes caused by changes in even a single gene."
The following researchers were involved in the papers described above. To contact any of the researchers, please call one of the media contacts above.
- Jim Olson — Fred Hutchinson Cancer Research Center, Seattle, WA
- Ruth Luthi-Carter — Massachusetts General Hospital, Charlestown, MA
- Ed Chan — Center for Molecular Medicine and Therapeutics, Department of Medical Genetics, Children's and Women's Hospital, University of British Columbia, Vancouver, BC, Canada
- Andrew Lieberman — Department of Pathology, University of Michigan, Ann Arbor, MI
- Elena Cattaneo — Department of Pharmacological Sciences and Center of Excellence on Neurodegenerative Diseases, University of Milano, Milan Italy
- Kenneth Fischbeck — Branch Chief, Neurogenetics, NINDS, NIH, Bethesda, MD
- Michael Hayden — Department of Medical Genetics, Center for Mol. Med. & Therapeutics, University of British Columbia, Vancouver, BC, Canada
Fred Hutchinson Cancer Research Center
(617) 441-3030 x228
Hereditary Disease Foundation
# # #
Fred Hutchinson Cancer Research Center
The Fred Hutchinson Cancer Research Center, home of two Nobel Prize laureates, is an independent, nonprofit research institution dedicated to the development and advancement of biomedical technology to eliminate cancer and other potentially fatal diseases. Fred Hutchinson receives more funding from the National Institutes of Health than any other independent U.S. research center. Recognized internationally for its pioneering work in bone-marrow transplantation, the center's four scientific divisions collaborate to form a unique environment for conducting basic and applied science. Fred Hutchinson, in collaboration with its clinical and research partners, the University of Washington Academic Medical Center and Children's Hospital and Regional Medical Center, is the only National Cancer Institute-designated comprehensive cancer center in the Pacific Northwest and is one of 38 nationwide. For more information, visit the center's Web site at www.fhcrc.org.
3rd Millennium Inc., located in Cambridge, MA is a leading bioinformatics consultancy that works with pharmaceutical, biotech, and academic clients on a project basis to design and develop software systems critical to early stage biological research and discovery. 3rd Millennium's expertise is in custom biological database applications, microarray informatics and analytics, and data and analysis integration. The company has extensive experience developing systems for laboratory information management, microarray-based gene expression profiling, gene analysis and annotation, genomic and proteomic data integration and versioning, and biological pathway modeling. Additional information can be found at http://www.3rdmill.com.
Affymetrix is a market leader in creating breakthrough tools that are driving the genomic revolution. By applying the principles of semiconductor technology to the life sciences, Affymetrix develops and commercializes systems that enable scientists to improve the quality of life. The Company's customers include pharmaceutical, biotechnology, agrochemical, diagnostics and consumer products companies as well as academic, government and other non-profit research institutes. Affymetrix offers an expanding portfolio of integrated products and services, including its integrated GeneChip platform, to address growing markets focused on understanding the relationship between genes and human health. Additional information on Affymetrix can be found at www.affymetrix.com.
Hereditary Disease Foundation
The Hereditary Disease Foundation, established in 1968, initiated and coordinated the search that localized the Huntington disease gene in 1983 and the collaborative Research Group which isolated the gene after a decade long search. The HDAG is one of the many projects the HDF sponsors. The HDF supports cutting edge science, including the development of mouse models, studies of protein-protein interactions, strategies for gene therapy, and intercellular signaling in striatal neurons. Through grants, contracts, post-doctoral fellowships, and its interdisciplinary workshop program, the Foundation continues to build a research community committed to the cure of Huntington's disease and related disorders. Further information can be obtained from the Foundation's website at www.hdfoundation.org.