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New Scientific Theory May Change How Treatments For Inherited Neurodegenerative Diseases Are Developed

Date:
July 13, 2000
Source:
University Of Toronto
Summary:
Researchers at The Hospital for Sick Children and the University of Toronto propose a new theory for what causes neurons to die in inherited neurodegenerative diseases such as Huntington's and Parkinson's.

A team of researchers led by The Hospital for Sick Children and the University of Toronto has shown that what scientists thought caused neurons to die in inherited neurodegenerative diseases such as Huntington's and Parkinson's is in fact not the case. The scientists propose a new model for neuronal cell death in the July 13 issue of the journal Nature, which will lead to new research into treatments for these types of diseases.

Neurons are the cells of the nervous system that carry information to and from the brain. Once they have matured, normal neurons live forever, and don't die unless they are damaged. Neurodegenerative diseases are characterized by a progressive loss of cells from one region of the nervous system. Nerve cells cannot be replaced, and humans can only lose a certain number, before they start having noticeable symptoms, such as tremors in Parkinson's patients.

Previously, it was believed that the mutant genes in these inherited conditions caused cumulative damage to the neurons, damage from which they eventually died, much like how the aging process leads to death in humans. This study, which used data from patients with retinal degeneration, Huntington's disease and Parkinson's disease, showed that cumulative damage theory was not correct.

"I generated mathematical equations that predicted how fast neurons would die if accumulated damage caused cell death. These equations allowed me to study neuronal death that had been observed by other investigators. I found that their data wasn'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," said Geoff Clarke, the study's lead author and a graduate student at U of T working under the supervision of Dr. Roderick McInnes, head of the Developmental Biology Research Program at The Hospital for Sick Children Research Institute.

This new model to explain nerve cell death in inherited neurodegenerative diseases - the mutant steady state model - shows that the mutant genes are conferring a small but definite increase in risk that the cell could suddenly undergo programmed cell death.

"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. The significance is that any cell that can be saved by treatment is likely to function normally, since that cell isn't sick," said Dr. McInnes, the study's senior author, a professor of Molecular and Medical Genetics and Paediatrics at U of T and holder of the Anne and Max Tanenbaum Chair in Molecular Medicine at The Hospital for Sick Children.

This new theory means that researchers will now try to target the factors that lead to the increased risk of neuronal death, which is 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," Dr. McInnes added. "And while we did not specifically study all neurodegenerative diseases, we suspect that these finding may also apply to others like ALS (Lou Gehrig's disease) and Alzheimer's disease."

Other collaborators in this study include Dr. Richard Collins from the Department of Molecular and Medical Genetics at U of T, Dr. Charles Lumsden from the Institute of Medical Science at U of T, and Drs. Blair Leavitt and Michael Hayden from Centre for Molecular Medicine and Therapeutics at the University of British Columbia.

This research was supported by grants from 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.

CONTACT:
Helen Simeon, Public Affairs
The Hospital for Sick Children
(416) 813-6380
helen.simeon@sickkids.on.ca

Steven de Sousa, Public Affairs
University of Toronto
(416) 978-5949
steven.desousa@utoronto.ca


Story Source:

The above story is based on materials provided by University Of Toronto. Note: Materials may be edited for content and length.


Cite This Page:

University Of Toronto. "New Scientific Theory May Change How Treatments For Inherited Neurodegenerative Diseases Are Developed." ScienceDaily. ScienceDaily, 13 July 2000. <www.sciencedaily.com/releases/2000/07/000711143844.htm>.
University Of Toronto. (2000, July 13). New Scientific Theory May Change How Treatments For Inherited Neurodegenerative Diseases Are Developed. ScienceDaily. Retrieved August 1, 2014 from www.sciencedaily.com/releases/2000/07/000711143844.htm
University Of Toronto. "New Scientific Theory May Change How Treatments For Inherited Neurodegenerative Diseases Are Developed." ScienceDaily. www.sciencedaily.com/releases/2000/07/000711143844.htm (accessed August 1, 2014).

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