"The article in Nature adds to the understanding of the mechanism of action of Flurizan, providing a molecular basis for its ability to slow the progression of Alzheimer's disease, as was demonstrated in previous human clinical studies"
Myriad Genetics' Alzheimer's Disease Drug Mechanism of Action Detailed in Nature Article
Myriad Genetics, Inc. (NASDAQ: MYGN) announced today that the mechanism of action of Flurizan(R) (tarenflurbil) -- its drug candidate for the treatment of Alzheimer's disease, is elucidated in the scientific journal Nature. The article, "Substrate-targeting Gamma-secretase Modulators," will be published in the June 12, 2008 issue of Nature.
Previous studies, in vitro, in animal models and in humans, have demonstrated that Flurizan selectively lowers toxic amyloid beta 42, and is the first member of a new class of drugs known as selective amyloid lowering agents (SALAs). Further, Flurizan has been shown to modify the processing of the amyloid precursor protein (APP) by the gamma secretase enzyme. The specific way in which Flurizan accomplishes this reduction in the toxic amyloid beta 42 had remained a mystery until now.
The Nature paper confirms the SALA properties of Flurizan and establishes the mechanism by which Flurizan modulates the APP-gamma secretase interaction. The authors demonstrate that the molecular target of Flurizan is the amyloid precursor protein itself -- the substrate of gamma secretase. Flurizan modifies the conformation of the APP molecule as it is bound to the gamma secretase complex. This change in the shape and/or position of APP in the complex results in cleavage by gamma secretase that produces shorter length, non-toxic amyloid beta fragments, such as amyloid beta 38 and amyloid beta 40. This exciting finding is novel in that most drugs target enzymes, blocking their function directly, but the substrate of an enzyme has not generally been seen as a drug target. These new findings are consistent with previous studies that show that Flurizan selectively lowers amyloid beta 42 by shifting the conformation of the APP/gamma secretase complex through allosteric binding.
"The article in Nature adds to the understanding of the mechanism of action of Flurizan, providing a molecular basis for its ability to slow the progression of Alzheimer's disease, as was demonstrated in previous human clinical studies," said Adrian Hobden, Ph.D., President of Myriad Pharmaceuticals, Inc. "The findings help explain why compounds like Flurizan can have a dramatic effect on lowering amyloid beta 42, the initiator of plaque formation in the human brain, and offer hope for the treatment 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. of 1684 patients from 131 investigator sites. Topline data from the trial is scheduled for reporting in June 2008, and a full analysis of the data will be presented at the Alzheimer's Association's International Conference on Alzheimer's Disease in Chicago on July 29, 2008.
Flurizan is a registered trademark of Myriad Genetics, Inc. in the United States and other countries.
Myriad Genetics, Inc. is a biopharmaceutical company focused on the development of novel healthcare products. The Company develops and markets predictive medicine products, and is developing and intends to market therapeutic products. Myriad's news and other information are available on the Company's Web site at www.myriad.com.