Study Defines Role of Flurizan in Reducing Production of Toxic Beta Amyloid
Myriad Genetics, Inc. (NASDAQ: MYGN)announced today that the mechanism of action of Flurizan® (tarenflurbil)-- its drug candidate for the treatment of Alzheimer's disease, iselucidated in the scientific journal Nature. The article,"Substrate-targeting Gamma-secretase Modulators," will be published in theJune 12, 2008 issue of Nature.
Previous studies, in vitro, in animal models and in humans, havedemonstrated that Flurizan selectively lowers toxic amyloid beta 42, and isthe first member of a new class of drugs known as selective amyloidlowering agents (SALAs). Further, Flurizan has been shown to modify theprocessing of the amyloid precursor protein (APP) by the gamma secretaseenzyme. The specific way in which Flurizan accomplishes this reduction inthe toxic amyloid beta 42 had remained a mystery until now.
The Nature paper confirms the SALA properties of Flurizan and establishesthe mechanism by which Flurizan modulates the APP-gamma secretaseinteraction. The authors demonstrate that the molecular target of Flurizanis the amyloid precursor protein itself -- the substrate of gammasecretase. Flurizan modifies the conformation of the APP molecule as it isbound to the gamma secretase complex. This change in the shape and/orposition of APP in the complex results in cleavage by gamma secretase thatproduces shorter length, non-toxic amyloid beta fragments, such as amyloidbeta 38 and amyloid beta 40. This exciting finding is novel in that mostdrugs target enzymes, blocking their function directly, but the substrateof an enzyme has not generally been seen as a drug target. These newfindings are consistent with previous studies that show that Flurizanselectively lowers amyloid beta 42 by shifting the conformation of theAPP/gamma secretase complex through allosteric binding.
"The article in Nature adds to the understanding of the mechanism of actionof Flurizan, providing a molecular basis for its ability to slow theprogression of Alzheimer's disease, as was demonstrated in previous humanclinical studies," said Adrian Hobden, Ph.D., President of MyriadPharmaceuticals, Inc. "The findings help explain why compounds likeFlurizan can have a dramatic effect on lowering amyloid beta 42, theinitiator of plaque formation in the human brain, and offer hope for thetreatment of patients who suffer from Alzheimer's disease."
Flurizan U.S. Phase 3 Clinical Trial
Flurizan has recently completed a Phase 3 clinical trial in the U.S. of1684 patients from 131 investigator sites. Topline data from the trial isscheduled for reporting in June 2008, and a full analysis of the data willbe presented at the Alzheimer's Association's International Conference onAlzheimer's Disease in Chicago on July 29, 2008.
Flurizan is a registered trademark of Myriad Genetics, Inc.
