Dec. 21, 2000 Researchers in the University of Toronto's Faculty of Medicine have discovered that a vaccine may help prevent and treat the disabling memory loss and cognitive impairment (dementia) of Alzheimer's disease.
Alzheimer's occurs when toxic biochemical compounds known as amyloid ß peptides accumulate in the brain, forming amyloid plaque deposits and injuring nerve cells, eventually causing dementia. While previous studies have shown that vaccinating transgenic mice with this peptide could remove the amyloid plaques, there was never any evidence of improvement in brain function.
After developing transgenic mice with amyloid plaques and cognitive impairment similar to those found in human Alzheimer's, scientists at U of T's Centre for Research in Neurodegenerative Diseases (CRND) determined that immunization with amyloid ß peptides blocked both the production of the plaques and learning impairment.
"Not only were we able to clean up the brain tissue, but we also prevented the behavioural consequences of Alzheimer's," says Dr. Peter St George-Hyslop, director of the CRND and a neurologist at the University Health Network. "Obviously, it is more important that a treatment or prevention in humans be able to block the clinical dementia."
St George-Hyslop and his colleagues say the amyloid ß peptide vaccination is ready to be tested on humans. "Our results also show that pharmaceutical treatments that are directed at blocking the formation of the peptide or that accelerate its removal might also be good ways to treat Alzheimer's either alone or in conjunction with other interventions like vaccination," says Christopher Janus, research associate at the CRND and the study's first author. "In the future there might be a cocktail of treatments including drugs which block formation and inhibit the toxicity and then a vaccination which will remove the plaque."
The researchers believe this study provides the final element of proof that Alzheimer's is initiated by amyloid ß peptides. "While there are other factors that play a role in the development of the disease, there is little doubt that these peptides initiate the process," says David Westaway, associate professor of laboratory medicine and pathobiology in the Faculty of Medicine and one of the study's co-authors. "If results from our laboratory studies hold true in humans, this vaccine might well play a key part in eradicating the disabling dementia that is associated with the disease, whether caused by genetic or environmental factors."
The next step will be for pharmaceutical manufacturers to conduct preliminary trials on the safety of the vaccination, before larger scale testing can begin on its therapeutic effectiveness. The researchers believe clinical trials could begin on human subjects within the year.
Over the past decade, researchers at U of T's Centre for Research in Neurodegenerative Diseases (http://www.utoronto.ca/crnd/) have made a number of fundamental discoveries which have had a significant impact on our understanding of Alzheimer's and other neurodegenerative diseases. Earlier this year they discovered a new gene, Nicastrin, involved in the biochemical processes involved in amyloid ß peptide production. In 1995 they identified two defective genes that cause aggressive early-onset forms of Alzheimer's (Presenilin 1 and Presenilin 2) and in 1990, they were the first to show Alzheimer's is a complex disorder with many causes, some of which are genetic.
This study, to be published in the Dec. 21-28 issue of Nature, was supported by the Alzheimer Society of Ontario, the Canadian Institutes of Health Research, The W. Garfield Weston Foundation, the Howard Hughes Medical Institute and the US National Institute of Aging.
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