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Test reveals effectiveness of potential Huntington's disease drugs
October 30, 2006A test using cultured cells provides an effective way to screen drugs against Huntington's disease and shows that two compounds - memantine and riluzole - are most effective at keeping cells alive under conditions that mimic the disorder, UT Southwestern Medical Center researchers report.
"These drugs have been tested in a variety of Huntington's disease models and some HD human trials and results are very difficult to interpret," said Dr. Ilya Bezprozvanny, associate professor of physiology and senior author of the study, available online and published in today's issue of Neuroscience Letters. "For some of these drugs conflicting results were obtained by different research groups, but it is impossible to figure out where the differences came from because studies were not conducted in parallel.
"We systematically and quantititatively tested the clinically relevant drugs side-by-side in the same HD model. That has never been done before," said Dr. Bezprozvanny.
Huntington's disease is a fatal genetic disorder, manifesting in adulthood, in which certain brain cells die. The disease results in uncontrolled movements, emotional disturbance and loss of mental ability. The offspring of a person with Huntington's have a 50 percent chance of inheriting it.
More than 250,000 people in the United States have the disorder or are at risk for it. There is no cure, but several drugs are used or are being tested to relieve symptoms or slow Huntington's progression.
The disease affects a part of the brain called the striatum, which is involved in the control of movement and of "executive function," or planning and abstract thinking. It primarily attacks nerve cells called striatal medium spiny neurons, the main component of the striatum.
Dr. Bezprozvanny's group previously demonstrated that Huntington's striatal neurons are oversensitive to glutamate, a compound that nerve cells use to communicate with each other.
In the latest UT Southwestern study, the researchers cultured striatal spiny neurons from the brains of mice genetically engineered to express the mutant human Huntington gene. As predicted, glutamate killed the Huntington's neurons, but the scientists also tested five clinically relevant glutamate inhibitors to assess their protective ability.
Folic acid has been suggested as a treatment for people with Huntington's because it interacts with homocysteine, a compound that makes nerve cells more vulnerable to glutamate. Gabapentin and lamotrigine, both glutamate inhibitors, are used in epilepsy treatment and as a mood stabilizer, respectively. These three compounds did not significantly protect the cultured cells.
However, a drug called memantine, which is used to treat Alzheimer's disease, and riluzole, used in amyotrophic lateral sclerosis, did protect the cells. Memantine demonstrated a stronger effect in the study. Memantine has also shown evidence of retarding the progression of Huntington's in people, while riluzole has helped relieve some symptoms.
"Our results provide the first systematic comparison of various clinically relevant glutamate pathway inhibitors for HD treatment and indicate that memantine holds the most promise based on its in vitro efficacy," Dr. Bezprozvanny said. "Whole animal studies of memantine in an HD mouse model will be required to validate these findings.\\\
UT Southwestern Medical Center
Huntington's disease is a fatal genetic disorder, manifesting in adulthood, in which certain brain cells die. The disease results in uncontrolled movements, emotional disturbance and loss of mental ability. The offspring of a person with Huntington's have a 50 percent chance of inheriting it.
More than 250,000 people in the United States have the disorder or are at risk for it. There is no cure, but several drugs are used or are being tested to relieve symptoms or slow Huntington's progression.
The disease affects a part of the brain called the striatum, which is involved in the control of movement and of "executive function," or planning and abstract thinking. It primarily attacks nerve cells called striatal medium spiny neurons, the main component of the striatum.
Dr. Bezprozvanny's group previously demonstrated that Huntington's striatal neurons are oversensitive to glutamate, a compound that nerve cells use to communicate with each other.
In the latest UT Southwestern study, the researchers cultured striatal spiny neurons from the brains of mice genetically engineered to express the mutant human Huntington gene. As predicted, glutamate killed the Huntington's neurons, but the scientists also tested five clinically relevant glutamate inhibitors to assess their protective ability.
Folic acid has been suggested as a treatment for people with Huntington's because it interacts with homocysteine, a compound that makes nerve cells more vulnerable to glutamate. Gabapentin and lamotrigine, both glutamate inhibitors, are used in epilepsy treatment and as a mood stabilizer, respectively. These three compounds did not significantly protect the cultured cells.
However, a drug called memantine, which is used to treat Alzheimer's disease, and riluzole, used in amyotrophic lateral sclerosis, did protect the cells. Memantine demonstrated a stronger effect in the study. Memantine has also shown evidence of retarding the progression of Huntington's in people, while riluzole has helped relieve some symptoms.
"Our results provide the first systematic comparison of various clinically relevant glutamate pathway inhibitors for HD treatment and indicate that memantine holds the most promise based on its in vitro efficacy," Dr. Bezprozvanny said. "Whole animal studies of memantine in an HD mouse model will be required to validate these findings.\\\
UT Southwestern Medical Center
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Test reveals effectiveness of potential Huntington's disease drugs
A test using cultured cells provides an effective way to screen drugs against Huntington's disease and shows that two compounds-memantine and riluzole - are most effective at keeping cells alive under conditions that mimic the disorder, UT Southwestern Medical Center researchers report.
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"Booster rocket" malfunction implicated in Huntington's disease
CNRS and Inserm research scientists at the Institut Curie have shed new light on the function of huntingtin, the protein whose mutation underlies Huntington's disease. This neurodegenerative disease, like Alzheimer's or Parkinson's, is characterized by the abnormal death of certain neurons. The scientists have discovered that huntingtin, like a "booster rocket", accelerates the transport of a neuron survival factor. When huntingtin is mutated, the "booster rocket" malfunctions, transport slows, protection wanes, and neurons die. This discovery, published in the 9 July 2004 issue of Cell, could in time lead to novel therapeutic methods of blocking the accelerated death of neurons.
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Huntington's disease (HD), a fatal degenerative disorder of the brain, can be alleviated by administration of a protein known to promote neuron survival, say scientists in the January's journal Experimental Neurology.
A new pathway for halting neuronal death in Huntington's disease
The body is an extremely complex puzzle in which every piece plays a critical role. Should pieces disappear harmony is compromised. Such is the case with certain neurodegenerative diseases; when neurons suddenly die, the body's ability to function properly is jeopardized. CNRS (1) and INSERM biologists from the Curie Institute are working to understand how neurons die in one specific neurodegenerative disease: Huntington's disease. They have just announced the discovery of two new factors capable of blocking cell death induced in Huntington's disease. They may eventually provide targets for the therapeutic treatment of this type of disease. These discoveries were published in the 7th of Ju
Patients' views about their illness can help treatment planning
What is it like to be chronically ill? Those people with severe illnesses such as Huntington's disease or multiple sclerosis do not see their illness in the same way as health professionals do. Associate professor Ad Kaptein, Leiden University, Netherlands organised an international symposium on patients' representations of their illnesses at the joint British Psychological Society's Division of Health Psychology and European Health Psychology Society conference held at St Andrews University, today, Wednesday 5 September. Health psychologists from Portugal, New Zealand, the Netherlands and the UK were discussing the following research. Multiple Sclerosis is a chronic, incurable and debili
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