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Sent: Tuesday, July 18, 2000 9:45 PM
Subject: Fw: Parkinson Disease - New Steady State Model Explains


> Interesting stuff.
>
> >
> >  New View of Neurodegenerative Diseases                     <>
> >
> >  >>> UPI
> >  >>> Tuesday, July 18, 2000
> >
> >  SAN FRANCISCO - A new view of the underlying mechanisms
> >  of Parkinson's, Huntington's, and other neurodegenerative
> >  diseases may result in novel treatments for them,
> >  researchers report.
> >
> >  Such disorders result from the premature death of nerve
> >  cells that appear to function normally to the end and not
> >  degenerate progressively, as has been thought, the
> >  investigators said.
> >
> >  "The significance of this work is that it completely
> >  reorients our understanding of neurological
> >  degenerations," said senior study author Roderick
> >  McInnes, professor of molecular and medical genetics and
> >  pediatrics at the University of Toronto in Ontario,
> >  Canada, and head of the Developmental Biology Research
> >  Program and holder of the Anne and Max Tanenbaum Chair in
> >  Molecular Medicine at The Hospital for Sick Children
> >  Research Institute.
> >
> >  The findings may influence how scientists conduct
> >  experiments and interpret their results in the field, and
> >  hold "important implications for the treatment as well,"
> >  McInnes told United Press International.
> >
> >  Researchers have long known the death of neurons, the
> >  nerve cells that carry messages to and from the brain, is
> >  behind Alzheimer's, Parkinson's and the sudden loss of
> >  motor function in patients suffering from amyotrophic
> >  lateral sclerosis, or ALS, better known as Lou Gehrig's
> >  disease.
> >
> >  While this common thread of cell fatalities has been
> >  shown to run through these and other neurodegenerative
> >  disorders, more detailed attempts to understand the
> >  factors that unite them have stumbled over such obstacles
> >  as their varying times of onset and clinical progression.
> >
> >  Might the neuronal loss in all of these diseases follow a
> >  common course? Or is the demise in each as individualized
> >  as some of the symptoms? The experimental evidence from
> >  the animal and cell culture studies of Parkinson's,
> >  Huntington's and retinal degeneration support a common,
> >  "one-hit" model of cell death in inherited
> >  neurodegenerative diseases.
> >
> >  The findings argue against the hypothesis that cell
> >  damage accumulates until it reaches lethal proportions,
> >  indicating instead that the time of death of any neuron
> >  is random.
> >
> >  "Our findings demonstrate that, for many neurological
> >  degenerations, the basic premise underlying the study of
> >  these diseases was incorrect," McInnes said. "That
> >  premise, designated 'the cumulative damage' model, is
> >  that the mutant neurons (in those neuronal degenerations
> >  which are genetic in origin) are initially in good
> >  health, but that they accumulate damage as the years go
> >  by. Eventually a critical amount of damage accumulates,
> >  and the cell dies."
> >
> >  Instead, "we found that they are at a constant increased
> >  risk of death, as soon as they are formed," McInnes said,
> >  adding that the treatment goal would be to return the
> >  risk to normal, i.e. zero, or at least to reduce it.
> >
> >  "The obvious implication for treatment is that, if the
> >  affected neurons are alive, they can be saved by any
> >  effective treatment that would function well for the life
> >  of the patient," McInnes said. "In the cumulative damage
> >  model the situation is quite different. In that case, you
> >  might apply treatment to a cell, but if its degeneration
> >  has progressed too far, it may never function normally
> >  again."
> >
> >  "These results are certain to stimulate much debate and
> >  experimentation, aimed both at identifying common
> >  mechanisms of neurodegeneration and at developing common
> >  ways of intervening in these tragic diseases," said
> >  Nathaniel Heintz of the Howard Hughes Medical Institute
> >  at the Rockefeller University in New York, who wrote an
> >  accompanying News and Views article in the British
> >  journal Nature.
> >
> >  While convinced of the strength of their data, the study
> >  authors conceded their model "might still be incorrect."
> >
> >  Unless damaged, normal neurons live as long as the body
> >  they inhabit. In neurodegenerative diseases, one region
> >  of the nervous system suffers a progressive loss of these
> >  irreplaceable cells. As the fatality count rises,
> >  patients begin to experience symptoms, such as the
> >  tremors characteristic of Parkinson's.
> >
> >  "The one-hit model proposes that the mutant neurons in
> >  inherited neurological degenerations are in general good
> >  health and function well, except for one thing: they are
> >  at an increased risk of dying compared to normal adult
> >  neurons (which generally don't die)," McInnes told UPI.
> >
> >  "The increase in risk of death is constant throughout the
> >  life of the individual, and the time at which death
> >  occurs is totally random. This model therefore predicts
> >  that cells in the affected parts of the brains of
> >  patients with these diseases will function well until the
> >  cells die. In fact, in those situations where function
> >  has been studied, as in retinal degenerations, that is
> >  exactly what has been found: if the cell is
> >  alive, it is
> >  well."
> >
> >  Geoff Clarke of the University of Toronto, lead author of
> >  the study published in Nature, generated mathematical
> >  equations predicting the speed of neuronal death caused
> >  by accumulated damage.
> >
> >  "These equations allowed me to study neuronal death that
> >  had been observed by other investigators," he said. "I
> >  found that their data weren't consistent with the idea of
> >  increasing amounts of cellular damage. Instead, our
> >  analysis demonstrated that neuronal cell death in
> >  neurodegenerative diseases occurs randomly during the
> >  life of the patient."
> >
> >  Taking their findings into account, McInnes, Clarke,
> >  Richard Collins of the Department of Molecular and
> >  Medical Genetics and Charles Lumsden of the Institute of
> >  Medical Science at the University of Toronto and Blair
> >  Leavitt and Michael Hayden of the Centre for Molecular
> >  Medicine and Therapeutics at the University of British
> >  Columbia devised the "mutant steady state model" to
> >  explain nerve cell death in inherited neurodegenerative
> >  diseases.
> >
> >  In this scenario, mutant genes confer a small but
> >  definite increase in risk of sudden programmed cell death
> >  in a perfectly normal, healthy cell, they said.
> >
> >  The picture of mutant neurons in neurological
> >  degenerations resembles that of very high cholesterol
> >  levels in a healthy-looking, athletic adult, the
> >  scientists said.
> >
> >  "He looks and feels well and to all appearance is fine.
> >  But he is at an increased risk of random death, if his
> >  coronary artery suddenly obstructs," McInnes said.
> >
> >  "Our work indicates that the neurons that are still alive
> >  are functioning well for years or decades and are not
> >  seriously damaged, but they are at increased risk of
> >  suddenly dying," he said. "The significance is that any
> >  cell that can be saved by treatment is likely to function
> >  normally, since that cell isn't sick."
> >
> >  If the new theory holds up, researchers could target
> >  whatever mechanism increases the risk of neuronal death
> >  caused by mutant genes.
> >
> >  "If we can identify what critical reactions in the
> >  neurons lead to the increased risk of programmed cell
> >  death, then we can try to push them back towards normal.
> >  This will be tough, but there are some candidate
> >  molecules that scientists have been investigating,"
> >  McInnes said. "And while we did not specifically study
> >  all neurodegenerative diseases, we suspect that these
> >  findings may also apply to others like ALS and
> >  Alzheimer's disease."
> >
> >  The scientists now want to determine whether the model
> >  applies to other neurological degenerations and to
> >  identify the critical biochemical abnormalities that put
> >  the neuron at risk of death.
> >
> >  "The ultimate aim is to identify the critical biochemical
> >  abnormalities in each disease and to learn how to reverse
> >  these abnormalities, thus taking the cell out of harm's
> >  way," McInnes said.
> >
> >  This may take years, he said.
> >
> >  "However, this model is a solid first step in a new
> >  direction, hopefully the right direction," McInnes said.
> >  "Maybe we will be lucky and be able to identify one or
> >  more of the critical reactions soon, and maybe some of
> >  the critical reactions will be the same in different
> >  diseases."
> >
> >  The work was funded by the Foundation Fighting Blindness,
> >  The Macular Vision Research Foundation, The RP Eye
> >  Research Foundation of Canada, the Medical Research
> >  Council of Canada, the Canadian Genetic Disease Network
> >  and the Huntington Disease Society of America.
> >
> >  - Copyright 2000 by United Press International. All
> >  rights reserved.
> >
> >              All Rights Reserved C NewsMax.com
> >
> >
> >
>