New trials of two Alzheimer drugs
Clinical trials of two experimental Alzheimer drugs, both being tested for their potential to counter basic biological missteps in the Alzheimer brain, have been announced by their corporate sponsors.
The first study, launched by Salt Lake City-based Myriad Pharmaceuticals, is a nationwide Phase III trial of Flurizan (MPC-7869), the company's pure "R" formulation of the nonsteroidal anti-inflammatory drug (NSAID) flurbiprofen (fler-bih-PROH-fin). Flurbiprofen is one of a handful of NSAIDs shown in laboratory and animal studies to reduce levels of beta-amyloid, a protein fragment considered a prime suspect in Alzheimer's disease.
Generic flurbiprofen is a mixture of "R" and "S" molecules whose structures are mirror images of one another. Flurizan contains only R-flurbiprofen, the form that seems to have the greatest impact on beta-amyloid but has little or no effect in blocking cyclooxygenase (COX) enzymes. Blocking activity of COX enzymes is among the chief anti-inflammatory mechanisms of NSAIDs but is associated with certain serious side effects, including bleeding in the stomach and intestines and increased risk of heart attack and stroke.
In the Flurizan Phase III trial, about 100 U.S. sites will enroll approximately 750 individuals with mild to moderate Alzheimer's disease. Participants will be randomly assigned to receive 400 or 800 milligrams of Flurizan twice daily or a placebo. The trial is designed to determine whether those assigned to either dose of Flurizan fare better in mental function or ability to carry out daily activities than those on the placebo. Trial details are posted in the federal online medical research database at ClinicalTrials.gov.
The second trial is a small Phase I study of AL-108, a drug in development by Vancouver-based Allon Therapeutics. AL-108 may help shield the brain against Alzheimer's and other disorders that cause nerve cells to deteriorate. AL-108 is a short section of subunits from a naturally occurring protein called activity-dependent neuroprotective protein (ADNP) whose function is to protect brain cells. Laboratory and animal studies suggest the small subsection may also offer significant protection.
The Phase I study, designed primarily to evaluate the safety of AL-108 and how it is processed in the body, will enroll 30 healthy Phoenix-area adults who will be randomly assigned to receive increasing doses of AL-108 or a placebo delivered through a nasal spray.
For more information, please see:
- An Aug. 5, 2003 Research News feature on R-flurbiprofen:
- The Alzheimer's Association fact sheet on the "amyloid hypothesis" and drugs targeting beta-amyloid
- The Alzheimer's Association fact sheet on anti-inflammatory drugs: