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Fasudil could reduce risk of Alzheimer's

Published on February 2, 2009 at 11:03 PM · No Comments

A drug used to improve blood flow to the brain also could help improve learning and memory and reduce the risk of Alzheimer's disease, according to a new study released today by investigators at the Translational Genomics Research Institute (TGen) and Arizona State University.

Fasudil has been used for more than 10 years to help protect the brain in stroke patients by dilating blood vessels when blood flow is curtailed.

Now, a team of Arizona psychologists, geneticists and neuroscientists report in today's edition of the journal Behavioral Neuroscience that hydroxyfasudil, the active form of the parent drug Fasudil, improved spatial learning and working memory in middle-aged rats when negotiating a complicated maze.

The findings suggest that hydroxyfasudil may influence similar cognitive processes in humans involving the hippocampus, a part of the brain that has been shown to deteriorate in patients with age-related disorders.

"If Fasudil proves to be safe and effective in enhancing learning and memory, it could represent a viable new option for the prophylactic treatment of disorders with a cognitive decline component. This could include diseases like Alzheimer's as well as general age-related impairment. In short, it may be a new pharmaceutical weapon that could be used even before the occurrence of symptoms," said Dr. Matthew Huentelman, an Investigator in TGen's Neurogenomics Division.

Clinical trials are being explored in the areas of cognitive impairment and dementia, said Huentelman, the scientific paper's first author.

Although far from proving anything about human use of the drug, the findings supports the scientific quest for a substance that could treat progressive cognitive impairment, cushion the impact of aging, or even enhance learning and memory throughout one's life span.

"Fasudil shows great promise as a cognitive enhancer during aging,'' said Dr. Heather Bimonte-Nelson, an Assistant Professor in ASU's Department of Psychology and the paper's lead author. "The effects in our aging-animal model were robust, showing enhancements in both learning and two measures of memory. The possibility that these findings may translate to benefits to human brain health and function is very exciting."

In the study, the researchers gave daily injections of hydroxyfasudil to middle-aged (17-18 months old) male rats, starting four days before behavioral testing and continuing throughout testing. Injection made it easy to give the drug to rats, but people take it in the form of a pill.

Rats were tested on a water radial-arm maze, which assessed how well they remembered which of the radiating arms had a reward, a sign of accurate spatial learning and working memory. Rats given a high dose (0.3750 mg per kg of weight) of hydroxyfasudil successfully remembered more items of information than those given a low dose (0.1875 mg per kg). Both dosed groups performed significantly better than control-group rats given saline solution. On this same test, the high-dose group showed the best learning (fewest total errors) and best working memory (measured two different ways).

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