Drug provides key to halting Alzheimer’s disease in mice

Researchers at the University of Toronto are one step closer to slowing or stopping the progression of Alzheimer’s disease. In a study published online in Nature Medicine, Professor JoAnne McLaurin and her colleagues David Westaway, Howard Mount, Paul Fraser and Peter St George-Hyslop at the Centre for Research in Neurodegenerative Diseases have identified a drug that stops the amyloid peptide which causes toxic neural damage in brains affected by Alzheimer’s disease from accumulating.

When the researchers orally administered a small molecule known as scyllo-cyclohexanehexol (AZD-103) to mice that had been genetically altered to have Alzheimer’s disease, they found that the drug prevents aggregates of the amyloid peptides from forming, thereby reducing the toxicity in the brain and preventing additional cognitive damage or memory loss. These benefits were apparent when the drug was administered to mice before they began to exhibit Alzheimer’s-like symptoms and after the symptoms had begun. This is a significant breakthrough in drug development for Alzheimer’s disease, says McLaurin. We have effectively demonstrated improvement in memory and pathology among mice and are cautiously optimistic that the same may hold true for human patients after formal clinical trials have been conducted.Based on the study’s results, Health Canada has approved the drug for Phase 1 Clinical Trials. Funded by the Ontario Research and Development Challenge Fund and administered by Transition Therapeutics Inc., the trials will determine whether the drug produces side effects in healthy humans. The study’s results are promising, but we must be aware of the fact that AZD-103 must be formally tested in humans to ensure that it is safe and effective, says University Professor Peter St George-Hyslop, director of the Centre for Research in Neurodegenerative Diseases. This is a long-term collaboration involving the University of Toronto and the Alzheimer Society of Ontario, supported by both federal and provincial research funding organisations; if successful, it will be an example of basic science being funded from the initial discovery through to a translational product that can be used by a Canadian company to improve the quality of life for people with Alzheimer’s.AZD-103 should not be confused with the health food substance myo-inositol or inositol, which the researchers have previously shown to be ineffective in treating Alzhiemer’s disease. Since 1990, the Centre for Research in Neurodegenerative Diseases has made several fundamental discoveries that have had significant impact on our understanding of Alzheimer’s and other neurodegenerative diseases. The centre’s researchers were the first to show that Alzheimer’s is a complex disorder with many causes, some of which are genetic; they have identified several genes associated with Alzheimer’s, including Presenilin 1 and Presenilin 2, which cause aggressive early-onset forms of Alzheimer’s. Most recently they discovered two other genes, Nicastrin and TMP21 that are also involved in the biochemical processes of amyloid peptide production. (Source: Nature Medicine: University of Toronto: June 2006).