Tamara Kopp, 18 yrs Tamara Kopp, 34 yrs
Although Tami showed signs of illness at the age of 18 she was not diagnosed with Huntingtons disease until she was 24 yrs old.
HD Research - Past and Future
There has been an explosion of Huntington's Disease research since the gene was discovered in 1993. The discovery of the gene was the culmination of ten years of work by more than fifty collaborators in six labs and it represents a critical milestone in the effort to understand and treat the disease. As Dr. James Gusella, Coalition for the Cure researcher and member of the gene discovery team, has said, once the gene was found, the research could begin in earnest.
Huntington's Disease is caused by a genetic stutter in a gene that produces a large protein found in animals from yeast to humans. Its functions are not yet fully understood. There is a section of the gene that encodes for glutamine; the code consists of a series of the base pairs cytosine, adenine, and guanine (CAG repeats). In the Huntington's gene, these CAG triplets occur an abnormal number of times, changing the protein in ways that challenge the medium spiny neurons in the brain. Since the discovery of the HD gene, the genes for eight other polyglutamine disorders have been discovered.
Much has been learned about where and how the HD protein causes its damage. The most cell death occurs in the striatum but the cortex is affected too and cortical dysfunction has emerged as a major source of pathology.
The Huntington's Disease protein has been found to affect hundreds of cellular processes and components but several areas appear to be critical, including impaired protein folding and clearance, reduced cellular metabolism, neurotransmission problems, fragmentation of the protein and nuclear aggregation, and dysregulation of gene transcription with some genes being underexpressed and some overexpressed. Two of the affected genes which play a role in HD pathology include Brain Derived Neurotrophic Factor (BDNF) which is down-regulated and P53 which is up-regulated.
Much of what we now know about how Huntington's Disease develops has come about as a result of the development of the transgenic mouse in 1996 by Gillian Bates. Only humans get Huntington's naturally, but Dr. Bates was able to produce this model by inserting a short fragment of the human gene including about 150 CAG repeats.
Today there are various mouse models and each one captures a somewhat different set of Huntington's symptoms. The models include ones in which the entire human HD gene have been inserted (transgenic, full length) and ones in which extra mouse CAG repeats have been added to the mouse's own huntingtin's protein gene (knock-in models).
Various pathogenic processes have been found in the HD mice and other models and confirmed in human HD, adding to our knowledge about the disease. The mice are also used to test potential treatments.
Rigorous research has shown conclusively that the disease can be modified by various treatments in mouse models. This gives rise to the hope that at least some of these drugs, supplements, and interventions will make it through the research pipeline and become available treatments for people with the HD gene within the next few years.
The mouse models and new technologies have made it possible to identify targets for drugs, supplements, and other interventions that might prevent, slow or reverse disease progression. Knowing where to intervene allows researchers to find existing drugs that affect the target and test them as potential treatments. It is also the first step in drug development.
There has been an explosion of Huntington's Disease research since the gene was discovered in 1993. The discovery of the gene was the culmination of ten years of work by more than fifty collaborators in six labs and it represents a critical milestone in the effort to understand and treat the disease. As Dr. James Gusella, Coalition for the Cure researcher and member of the gene discovery team, has said, once the gene was found, the research could begin in earnest.
Huntington's Disease is caused by a genetic stutter in a gene that produces a large protein found in animals from yeast to humans. Its functions are not yet fully understood. There is a section of the gene that encodes for glutamine; the code consists of a series of the base pairs cytosine, adenine, and guanine (CAG repeats). In the Huntington's gene, these CAG triplets occur an abnormal number of times, changing the protein in ways that challenge the medium spiny neurons in the brain. Since the discovery of the HD gene, the genes for eight other polyglutamine disorders have been discovered.
Much has been learned about where and how the HD protein causes its damage. The most cell death occurs in the striatum but the cortex is affected too and cortical dysfunction has emerged as a major source of pathology.
The Huntington's Disease protein has been found to affect hundreds of cellular processes and components but several areas appear to be critical, including impaired protein folding and clearance, reduced cellular metabolism, neurotransmission problems, fragmentation of the protein and nuclear aggregation, and dysregulation of gene transcription with some genes being underexpressed and some overexpressed. Two of the affected genes which play a role in HD pathology include Brain Derived Neurotrophic Factor (BDNF) which is down-regulated and P53 which is up-regulated.
Much of what we now know about how Huntington's Disease develops has come about as a result of the development of the transgenic mouse in 1996 by Gillian Bates. Only humans get Huntington's naturally, but Dr. Bates was able to produce this model by inserting a short fragment of the human gene including about 150 CAG repeats.
Today there are various mouse models and each one captures a somewhat different set of Huntington's symptoms. The models include ones in which the entire human HD gene have been inserted (transgenic, full length) and ones in which extra mouse CAG repeats have been added to the mouse's own huntingtin's protein gene (knock-in models).
Various pathogenic processes have been found in the HD mice and other models and confirmed in human HD, adding to our knowledge about the disease. The mice are also used to test potential treatments.
Rigorous research has shown conclusively that the disease can be modified by various treatments in mouse models. This gives rise to the hope that at least some of these drugs, supplements, and interventions will make it through the research pipeline and become available treatments for people with the HD gene within the next few years.
The mouse models and new technologies have made it possible to identify targets for drugs, supplements, and other interventions that might prevent, slow or reverse disease progression. Knowing where to intervene allows researchers to find existing drugs that affect the target and test them as potential treatments. It is also the first step in drug development.
Woody Guthri was a storyteller who used music to tell his stories. His work ranged from social commentaries about the working conditions of migrant workers and the urban poor to ballads and children’s songs. In 1967, Woody Guthrie, lost his battle with HD. He was just 55 years old. During the more than 15 years that the disease affected him, he struggled to continue to communicate his conviction that every man, woman and child has within them the power to make a difference.Soon after his death, his widow Marjorie vowed to do something about this silent killer. At the time, little was known about the disease. Marjorie placed a small ad in a New York City newspaper and slowly gathered a determined handful of volunteers and HD families from across the United States. From that first moment, when Marjorie Guthrie reached out to other HD families, a worldwide movement began that would change the lives of those living with HD and bring hope to families.Dynamic and compelling, Marjorie Guthrie convinced then President Jimmy Carter to form a Presidential Commission to study neurological diseases, including HD. The recommendations that resulted from that 1977 report have served as the cornerstone of HDSA’s commitment to the care and cure of HD. In 1983, HDSA Coalition for the Cure investigator, Jim Gusella, found the very first marker for the disease and, after a ten year search that involved collaboration among the top HD researchers worldwide, the gene was located on the short arm of chromosome 4. Since that time, research has progressed rapidly and, in 2004, HDSA formed a pipeline for drug discovery that begins in the laboratory with basic science (HDSA Grants & Fellows program and the prestigious HDSA Coalition for the Cure) progresses to applied/transitional research (HDSA partner CHDI) and then moves to patient’s bedside in the form of human clinical trials that test the most promising compounds often at HDSA Centers of Excellence. Today the question our families ask is not “if” there will be a treatment or cure, but “when.”In the area of care, HDSA has created a national network of resources and referrals that are unmatched by any other HD organization. HDSA Centers of Excellence provide medical and social services to those affected by HD and their families while a toll free helpline and extensive national web site (www.hdsa.org) help to provide access to services. HDSA chapters, affiliates, regions, social workers, and support groups work in tandem with the Centers of Excellence to increase awareness about HD and raise funds for research, education and family services.Marjorie Guthrie died just a few months before the marker was found in 1983. But in the 16 years that she worked to bring this disease out of the family closet, she brought empathy and hope – a hope for a future free of HD- to those affected by this devastating disease. Her work resulted in what is today the Huntington’s Disease Society of America http://www.hdsa.org/. HDSA is dedicated to completing the work that this courageous woman started.
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