Myriad Genetics' Alzheimer's Disease Drug Candidate Cuts Production of Key Senile Plaque Initiator
corporate-ir.net
- New Study Strengthens Myriad's Strategy of Preventing Cognitive Decline in Alzheimer's Disease -
SALT LAKE CITY, Aug. 5 /PRNewswire-FirstCall/ -- Myriad Genetics, Inc. (Nasdaq: MYGN), announced today that its Alzheimer's disease candidate drug, MPC-7869 (R-flurbiprofen) reduces levels of Abeta42 more effectively than any other compound tested, according to a new study. Abeta42 is the primary constituent of senile plaques that accumulate in the brains of patients with Alzheimer's disease. It is thought to be the key initiator of Alzheimer's disease since this peptide has the tendency to aggregate, cause neuronal damage and initiate amyloid deposits in the brain. Myriad believes that lowering the toxic Abeta42 peptide is a highly promising area of anti-Alzheimer's disease drug development, and MPC-7869 is now in a 200-patient Phase II human clinical trial.
The study was led by Jason Eriksen, Ph.D., a member of the research group headed by Todd Golde, M.D., Ph.D., of Mayo Clinic, Jacksonville together with collaborators from the research group headed by Edward Koo, Ph.D., at the University of California, San Diego, and product development scientists Kevin Jessing, Ph.D. and Kenton Zavitz, Ph.D. of Myriad Genetics. The results of the study were reported in an article published in the August 2003 issue of the Journal of Clinical Investigation, 112(3):440-449, jci.org entitled, "NSAIDs and Enantiomers of Flurbiprofen Target Gamma-Secretase and Lower Abeta42 In Vivo". The study demonstrates that only a select minority of non-steroidal anti-inflammatory drugs (NSAIDs) lower levels of the Abeta42 peptide, and among those few compounds, R-flurbiprofen was shown to be most effective by selectively targeting gamma-secretase without inhibiting its essential biological functions, and exhibiting an unequalled ability to lower Abeta42 in vitro and in an animal model. The study concludes that, "Because R-flurbiprofen reduces Abeta42 levels by targeting gamma-secretase and has reduced side effects related to inhibition of cyclooxygenase (COX), it is an excellent candidate for clinical testing as an Abeta42 lowering agent."
"We have long known that the use of NSAIDs is associated with a reduced risk of Alzheimer's disease," said Adrian Hobden, Ph.D., President of Myriad Pharmaceuticals, Inc. "Recently, this association has been shown to correspond with some, but not all NSAIDs, and the recent failure of Naproxen and Rofecoxib to prevent cognitive decline, reported in the Journal of the American Medical Association, is a striking example of the selective capability of this drug class. The lack of Abeta42 lowering in these two compounds is consistent with, and was anticipated by, the widely held hypothesis that Abeta42 is a chief culprit in Alzheimer's disease and that reduction of Abeta42 is an essential feature of an NSAID's ability to prevent the devastating cognitive decline of Alzheimer's disease."
Todd Golde, M.D., Ph.D., of Mayo Clinic, Jacksonville, commented, "Only eight of the twenty NSAIDs tested showed the ability to lower Abeta42 levels in vitro and many of these drugs are known to have serious gastrointestinal side effects associated with COX inhibition. However, R-flurbiprofen does not inhibit COX and has a pronounced ability to reduce levels of Abeta42, which makes it stand apart from the drugs tested as a promising drug candidate for lowering Abeta42 levels and potentially, the prevention of cognitive decline in Alzheimer's disease."
Alzheimer's disease is an important focus of Myriad's drug development efforts. Myriad is conducting a Phase II human clinical trial in Alzheimer's disease that will assess the efficacy of MPC-7869 (R-flurbiprofen) in reducing the cognitive decline in Alzheimer's patients. MPC-7869 has been shown to be effective in lowering levels of Abeta42 in cellular assays and in animal models. Myriad believes that MPC-7869 is the first well-tolerated drug that inhibits the production of Abeta42 to be evaluated in a clinical trial for the treatment of Alzheimer's disease. Myriad and Mayo Clinic are collaborating on the development of novel Alzheimer's disease therapeutics based upon several lead compounds that have been discovered at Mayo Clinic.
Link to full text, not sure how long this will remain valid:
jci.org |
