Myriad Genetics Inc has submitted an Investigational New Drug (IND) application for the evaluation of its drug, R-flurbiprofen, for the treatment and prevention of Alzheimer's disease, the Company announced today. In the submitted Phase I trial, Myriad will establish the safety profile and dosing regimens of R-flurbiprofen in healthy elderly volunteers.
The trial's principal investigators are Alzheimer's disease experts Drs. Todd Golde and Neill Graff-Radford of Mayo Clinic Jacksonville (Florida) and Drs. Edward Koo and Doug Galasko of the University of California San Diego. The study is designed to enroll 48 subjects and to be completed within 12 months, inclusive of enrollment, and is co-sponsored by the National Institute on Aging under a grant to Dr. Edward Koo at UCSD. Myriad holds an issued United States Patent and has several patent applications pending on the use of R-flurbiprofen in the prevention and treatment of Alzheimer's disease.
Alzheimer's disease is a degenerative neurological condition affecting up to 20% of all people aged 80 or older, with an estimated 4 million cases in the United States alone. Current approved treatments, such as acetylcholinesterase inhibitors, temporarily mitigate symptoms without meaningfully impacting progression of the underlying disease. Alzheimer's disease is marked by progressive cognitive decline and by the accumulation of amyloid plaques and neurofibrillary tangles in the brain. The major structural component of these plaques is amyloid beta protein, specifically Amyloid beta-42 (Ab42). Many researchers now believe that Ab42 plays an important role in the onset of Alzheimer's disease. Current research is focused on compounds that decrease levels of Ab42 with the hope of preventing or slowing the progression of Alzheimer's disease.
An epidemiological study of 7,983 patients, conducted by Dr. Bruno H.C. Stricker and colleagues of Erasmus Medical Center, Rotterdam, Netherlands, indicated that long-term use of certain nonsteroidal anti-inflammatory drugs (NSAIDs) could reduce the likelihood of developing Alzheimer's disease by 80%. As reported at the 8th International Conference on Alzheimer's Disease and Related Disorders in July 2002, further analysis of the Rotterdam study revealed that decreased risk of Alzheimer's disease appeared to correspond only with those NSAIDs which lowered the production of Ab42. Preclinical studies performed with NIH funding, at Mayo Clinic Jacksonville and UCSD have demonstrated that R-flurbiprofen substantially lowers the levels of Ab42 in both human cell lines and in animal models of Alzheimer's disease. These results further indicated that R-flurbiprofen lowers Ab42 more dramatically than NSAIDs.
Additional in vitro research conducted by Dr. Greg Cole and colleagues at the University of California Los Angeles (UCLA), and presented at the 8th International Conference on Alzheimer's Disease and Related Disorders, further support the potential clinical utility of R-flurbiprofen. The study found that R-flurbiprofen limited production of Ab42 and also of two other proteins implicated in the formation of plaques. Of the drugs tested, Dr. Cole specifically singled out R-flurbiprofen concluding that, "Because of this triple efficacy and low side-effect profile, R-flurbiprofen shows potential for clinical trials aimed at Alzheimer's disease prevention or treatment."
Upon successful completion of Myriad's Phase I study, Myriad plans to initiate a subsequent Phase II human clinical trial to evaluate the ability of R-flurbiprofen to prevent cognitive decline in patients suffering from either early Alzheimer's disease or mild cognitive impairment (MCI), a less severe disease that primarily affects memory. Sixty percent of patients with MCI progress to Alzheimer's disease within five years of diagnosis. Additional ongoing studies are evaluating the impact of long-term administration of R-flurbiprofen on cognitive impairment in a mouse model of Alzheimer's disease.