----- Original Message ----- From: <[log in to unmask]> To: <[log in to unmask]> 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 > > > > > > >