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SCIENTISTS DEVELOP FIRST MOUSE MODEL TO REPRODUCE CARDINAL FEATURES OF HUNTINGTON DISEASE
Vancouver - May 27, 1999: A team of researchers at the Centre for Molecular Medicine and Therapeutics, led by Dr. Michael Hayden, Scientific Director of the Canadian Genetic Diseases Network, has spearheaded a breakthrough in the study of the neurological disease, Huntington disease (HD).
The scientists, in collaboration with colleagues at the University of British Columbia, University of Toronto, and in the United States have produced yeast artifical chromosome (YAC) transgenic mice expressing the cardinal features of HD.
Huntington disease is associated with a gradual deterioration of brain cells which leads to onset of personality change, involuntary movements, and dementia typically between the ages of 35 and 45, and eventual death. In the study, the team produced mice expressing normal and mutant huntingtin protein in a developmental and tissue-specific manner identical to that observed in Huntington disease. The mutant mice show early electrophysiological abnormalities indicating cytoplasmic dysfunction prior to indications of neurodegeneration, then show selective degeneration of those specific neuronal cells that die in patients with HD. The results of the study are published today in the scientific journal Neuron.
Dr. Hayden commented that the new YAC mouse allows scientists to dissect the natural history of HD. In producing animals with the behavioral, electrophysiological and pathological characteristics of different stages of development of the disease, his team now has insights into the sequence of cellular and molecular events underlying the pathogenesis of HD. The discovery, which was supported by CGDN, the Medical Research Council of Canada, the Huntington Disease Society of America, and the National Institute of Health, will allow scientists to assess therapeutic strategies to delay or prevent the disease.
The Centre for Molecular Medicine and Therapeutics is a core research centre of the Children's and Women's Health Centre of B.C. and the Canadian Genetic Diseases Network. It is an innovative and unique partnership among Merck Frosst Canada Inc., the government of B.C., the University of British Columbia, and the Health Centre dedicated to the conduct of advanced research using novel approaches in molecular and cell biology and genetics, to obtain fundamental advances in knowledge.
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CANADIAN SCIENTISTS MAKE TWO ADVANCES IN GENETIC DISEASE RESEARCH
Vancouver: January 28, 1998: Two teams of scientists with the Canadian Genetic Diseases Network (CGDN), headquartered in Vancouver, will publish the results of important research findings in the February 1 issue of the scientific journal, Nature Genetics.
Dr. Guy Rouleau of Montreal General Hospital heads an international team which has discovered the gene and defined a previously unknown muta tion responsible for a debilitating muscle disease. Known as oculopharyngeal muscular dystrophy (OPMD), the condition typically strikes vic tims after age 60 and, in 90% of cases, progresses with age from loss of eyelid muscle and difficulty in swallowing to general muscle weaken ing and inability to stand. Researchers report that it is the first time the mutation: short GCG repeat amplifications which would lead to an enlarged poly alanine tract in a protein, have been seen.
A high incidence of OPMD carriers in Canada, 1 in 1,000, is found in Quebec. It is believed that almost 100% of carriers of the gene eventu ally develop the disease and pass the condition on to half of their children; therefore, the long term significance of Dr. Rouleau's discov ery is crucial. "Within a few months, a simple blood test will be available to diagnose accurately and easily if a person is a carrier of t he OPMD gene", he said. "We will also be able to offer a pre-symptomatic diagnosis which was not previously available", he added. The next step is to move towards finding a treatment for the disease.
In another Nature Genetics paper, Dr. Michael Hayden, Scientific Director of CGDN and the Centre for Molecular Medicine and Therapeutics in Vancouver, reports on new research findings which may assist in reducing human susceptibility to a class of devastating hereditary neurological diseases, in particular Huntington disease (HD). The advance was made in collaboration with CGDN scientist, Dr. Frank Tufaro, at the Un iversity of British Columbia, and Dr. Dale Bredesen at the Burnham Institute in California.
HD is associated with a gradual deterioration of brain cells which leads to the onset of disease symptoms typically between the ages of 35 a nd 45. The sequence of events which follows results in severe physical and behavioral deterioration and eventual death. The results of the study show the effects on cells of protein production by the mutated HD gene, and have found that the protein forms clumps in cells which i ncrease the body's susceptibility to a particular cell death process called 'apoptosis'. The discovery shows that there is a connection be tween the number of cells with clumps and the degree of cell death. The length of the protein itself influences the site in the cell where clumping occurs, and the shorter the protein, the worse the effect.
These insights provide new therapeutic directions for HD which include preventing shortening of the protein.
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CANADIAN SCIENTISTS REPORT NOVEL RESEARCH ON HEREDITARY NEUROLOGICAL DISORDERS
Vancouver - August 1, 1996: Scientists at the new Centre for Molecular Medicine and Therapeutics (CMMT) in Vancouver and at the Merck Frosst Centre for Therapeutic Research in Montreal have joined forces in developing a research strategy which may lead to genetic-based therapies for a class of devastating hereditary neurological diseases, in particular Huntington disease (HD).
HD is associated with a gradual deterioration of brain cells which leads to the onset of disease symptons typically between the ages of 35 and 45. The sequence of events which follows results in severe physical and behavioral deterioration and eventual death.
The new research, led by Dr. Paul Goldberg and Dr. Michael Hayden of CMMT in collaboration with Dr. Donald Nicholson of Merck Frosst, has found that an over production of protein by the HD gene is directly involved in a particular cell death process known as 'apoptosis', or cell suicide. Furthermore, the research indicates that the genetic mutation causing HD directly influences how this protein participates in apoptosis. Until now it has not been known how the DNA change in the disease caused nerve cells to die.
The results are published in the August 1 issue of the science journal Nature Genetics.
The findings offer a new rational basis for developing treatment strategies for people at risk for HD. To date, the research team has been successful in conducting prototype experiments using protein inhibitors developed by Merck Frosst. The challenge now is to develop drugs which could be used in the treatment of human patients suffering from HD.
The CMMT is a unique research initiative based on an agreement between the University of British Columbia and the B.C. Children's Hospital, and a $15 million operating grant from CGDN industry partner, Merck Frosst Canada Inc. CGDN played a key role in the establishment of CMMT and provides funding support for research in Huntington disease. Dr. Hayden, Director of CMMT is Scientific Director of the Canadian Genetic Diseases Network and a Professor of Medical Genetics at UBC.
This discovery, based on a productive collaboration between scientists in universities and industry, exemplifies how results can be accelerated by academic and industry laboratories working together. Without this partnership the research results would have taken much longer.
The goal of CMMT is to use new technology in understanding the mechanisms which cause disease with a genetic basis. CMMT scientists will work in collaboration with researchers worldwide, including the Canadian Genetic Diseases Network, a consortium of 37 of Canada's leading geneticists who are linked with 11 universities, 8 hospitals, and 10 core technology facilities across the country. The Network performs leading-edge research on common genetically transmitted diseases and works with industry partners on methods of detection and treatment of the diseases. Core funding for Network programs is provided by the federal Networks of Centres of Excellence Program through the Medical Research Council of Canada.
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A FIRST IN HUNTINGTON DISEASE RESEARCH: Scientists discover new functions of the HD gene
Vancouver - June 2, 1995: A group of researchers led by Dr. Michael Hayden, Scientific Director of the Canadian Genetic Diseases Network, has produced the first-ever mouse with a defect in the Huntington disease gene. These findings add important novel insights into the role the HD gene plays in causing the disease.
The research results are published in the June 2, 1995 issue of the scientific journal Cell. The paper describes Dr. Hayden's approach to understanding the functions of the HD gene by producing a "knock out" mouse where specific parts of the gene are deleted in every cell.
Since the discovery in 1993 of the genetic defect which causes Huntington disease, research teams around the world have been attempting to unlock the sequence of events which results in deterioration of brain cells, severe behavioral disturbance, involuntary movements, and eventual death in individuals who inherit DNA changes in the HD gene. How the gene causes the disease remains unknown. Mice models of disease are used to understand the disease process and to devise and test possible therapies.
Dr. Jamal Nasir, a principal scientist in the team, believes this new information indicates that an entirely new area in the brain may play a crucial role in the pathology of the disease. Said Dr. Nasir "This specific region of the brain has generally been overlooked by scientists for many years, so our new discovery about the functioning of the gene has raised the exciting possibility that this new area of the brain is very important in the development of Huntington disease".
Last year Hayden's team identified the HD gene in the mouse and, until now, has been working non-stop to create mice with changes in the HD gene. Noted Dr. Nasir, "The mice carrying one specific HD defect have problems switching behavioural strategies and are hyperactive. Their brains also show cellular damage in particular areas not usually studied in Huntington disease". He added that, in addition, mice with two changes in the HD gene die early in development, thus clearly demonstrating that this gene plays a crucial role in growth and development.
Dr. Anthony G. Phillips, Head of the Department of Psychology and a member of the UBC research team observed "these findings not only add to our understanding of Huntington disease, but also show that the complex relationship between brain and behaviour is open to genetic analysis".
The team's latest findings mean that the new HD mouse can be used to test a wide variety of existing drugs along with drugs under development to assess the impact of possible therapies. Commented Dr. Hayden, "This is another step forward in a greater understanding of Huntington disease. We are hopeful that future studies will make it possible to identify approaches to treatment for people afflicted with this disease".
Huntington disease is a devastating inherited neurological condition which usually starts in mid-life and leads to death after progressive deterioration of brain cells and brain function over 10-15 years.
Dr. Hayden's milestone research was supported through the funding and core technology facilities of the Canadian Genetic Diseases Network, one of Canada's Federal Centres of Excellence networks. This work was performed at the University of British Columbia in collaboration with faculty in six departments, four affiliated with the Faculty of Medicine. The newly established Centre for Molecular Medicine and Therapeutics in Vancouver was also involved in some aspects of the work.
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(Extracted from UBC Reports)
STUDY REVEALS NEW RISK GROUP FOR HUNTINGTON DISEASE
Vancouver - July 14, 1994: Researchers under the co-ordination of UBC's Dr. Michael Hayden have developed a definitive test for Huntington disease (HD) and, in the process, may have discovered a previously unknown group in the general population who may be at increased risk of developing the disease.
While the gene that causes HD was discovered in 1993, there remained a question at that time of whether this gene was solely responsible for the worldwide distribution of Huntington disease. HD is found in all populations, but with varying frequencies. In people of Western European descent, for example, it occurs in about one in 10,000 but in people of Japanese, Finnish and black African descent it occurs in about one in 100,000 or 10 times less frequently. The current discovery indicates that a single molecular mechanism underlies HD worldwide. The discovery of a single cause allowed Dr. Hayden's team to develop a cheap, reliable test to accurately determine those at risk of developing HD.
Said Dr. Hayden "We also found that there may be a small proportion of the population that may be at risk that we did not know about previously." He explained that these genetic mutations in HD have been found to occur only in offspring of males who are usually over 30 years of age when they have had children who eventually develop the disease. The implications of this finding may be relevant for those planning a family.
Dr. Hayden highlighted the international co-operation among scientises that resulted in the study which was published recently as the lead article in the New England Journal of Medicine.
Dr. Hayden is Scientific Director of the Canadian Genetic Diseases Network which partly supports his research in Huntington disease. The Network is a consortium of 38 of Canada's leading geneticists who are linked with nine universities across Canada and 11 technology core technology facilities to form an "institute without walls". The network carries a mandate under the federal government's Networks of Centres of Excellence Program to perform leading-edge research and to work with industry partners on detection and treatment of genetically-transmitted disease.
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ADVANCE IN RESEARCH ON HUNTINGTON DISEASE
Vancouver - March 23, 1993: A UBC medical research team led by Dr. Michael Hayden, professor of Medical Genetics and Scientific Director of the Canadian Genetic Diseases Network, together with Dr. Johanna Rommens of Hospital for Sick Children and the University of Toronto, has identified a rearrangement of genetic material in two patients with Huntington disease (HD). The research advance may explain a mechanism for the causation of HD.
An inherited disease of the brain, Huntington disease affects one person in 10,000 usually striking between the ages of 30 and 50 years. Onset of the disease, however, can occur anywhere from adolescence to old age. Approximately 12,000 - 15,000 Canadians are either affected or at high genetic risk of the disease which is characterized by abnormal movements, speech difficulties, behavioral disturbances, and intellectual impairment. Each child of an affected parent has a 50% chance of inheriting and developing Huntington disease.
Dr. Hayden and his group have been searching for the causes of HD for more than a decade. Some of his advances in HD research include developing the first prenatal predictive test for HD in 1986 and pioneering the first national program for HD testing in 1988. In working to identify the cause of the disease the team has isolated several other genes near the site of the HD gene, including the gene for myson light chain (a muscle protein), and adducin (a structural cellular protein). In 1981 Dr. Hayden published the first major medical and scientific reference book on Huntington disease.
Dr. Hayden's latest findings are published today in the international scientific journal Nature. Said Dr. Hayden, "This is a great day for families with Huntington disease. The accumulated data represents a significant step forward in our understanding of the disease."
The Canadian Genetic Diseases Network is a consortium of 38 of Canada's leading geneticists who are linked with nine universities across Canada and 11 technology core technology facilities to form an "institute without walls". The network carries a mandate under the federal government's Networks of Centres of Excellence Program to perform leading-edge research and to work with industry partners on detection and treatment of genetically-transmitted disease.