Scientists Seek to Block Progression of Alzheimer’s with Novel Medication that Targets the Source

Oregon Health & Science University is studying an experimental medication designed to prevent nerve damage and brain inflammation that can lead to progressive memory loss and behavioral changes in people with Alzheimer’s disease. Four-hundred volunteers nationwide with mild to moderate Alzheimer’s disease are being sought to further test this new approach.

Research shows the buildup of plaques can trigger brain inflammation in Alzheimer’s patients. A protein called beta amyloid accumulates in these plaque deposits and may damage nerve cells. Researchers are testing an experimental drug designed to prevent beta amyloid from binding to a brain-cell receptor known as RAGE (receptor for advanced glycation end products).

Cell receptors are like electrical sockets. Beta amyloid acts like a plug and attaches to the RAGE receptor and damage occurs, said Joseph Quinn, M.D., associate professor of neurology in the OHSU School of Medicine. “We believe this experimental drug covers up the receptor and protects the brain, just like the socket protectors a parent might use to baby-proof a house.”

“We're excited to be a part of this novel study, which is so promising that it has attracted the interest and support of both the pharmaceutical industry and the National Institute of Health,” Quinn added. “This is an indication that the drug has both good potential for success, and excellent science to support it. While most current Alzheimer’s disease therapies focus on the various symptoms of cognitive impairment, this trial is testing whether we can modify actual progression of the disease itself by targeting the interaction between amyloid beta and an important receptor in the brain.”

The industry-sponsored study is being conducted by the Alzheimer’s Disease Cooperative Study, a consortium of leading researchers supported by the National Institute on Aging, part of National Institutes of Health. The Disease Cooperative, headquartered at the University of California, San Diego will coordinate the 18-month, double-blind, placebo-controlled clinical trial under the direction of Douglas Galasko, M.D., professor of neurology at UCSD. The drug, which has been tested in animals and in preliminary human studies, is being studied in this Phase II clinical trial to determine if it will slow the progressive decline associated with Alzheimer’s disease.

Researchers hope to recruit 400 volunteers aged 50 and up at 40 sites nationwide, including Oregon Health & Science University. The ADCS consortium is a public resource, supported by the NIA, to facilitate the study of potential new therapies for Alzheimer’s disease. Its nationwide outreach is critical to the recruitment of participants into such studies.

“Progress in treating and preventing Alzheimer’s would just not be possible without the dedication of the patients and families who volunteer for clinical trials,” said Neil Buckholtz, Ph.D., chief of the NIA Dementias of Aging Branch.

Physicians and nurses will monitor the participants during regular visits and measure the severity and progression of disease using standard tests of functional and cognitive abilities. To ensure unbiased results, neither the researchers conducting the trial nor the participants will know who is receiving the study drug – known as PF 04494700 – and who is getting the placebo. Participants will be randomly assigned to one of three groups: Two groups will receive different doses of the experimental drug and the third group will receive a placebo (an identical inactive pill).

“In addition to monitoring disease progression through cognitive tests, we will examine various biological markers of the disease,” Galasko said. “These include the degree of atrophy (or shrinkage) of the brain as measured by an MRI, the extent of amyloid buildup in the brain assessed by Positron Emission Tomography imaging, and levels of amyloid beta and other proteins in blood and spinal fluid.”

Much of the preclinical, basic research connecting RAGE to amyloid beta that led to the current study was performed by scientists at Columbia University, the University of Perugia in Italy and the University of Magdeburg in Germany.

To learn how to participate in the study, contact NIA’s Alzheimer’s Disease Education and Referral Center at 1-800-438-4380 or by email to adear@nia.nih.gov. To view a list of the research sites or for information on dementia and aging, go to http://www.nia.nih.gov/Alzheimers.

About OHSU
Oregon Health & Science University is the state’s only health and research university, and Oregon’s only academic health center. OHSU is Portland's largest employer and the fourth largest in Oregon (excluding government), with 12,400 employees. OHSU's size contributes to its ability to provide many services and community support activities not found anywhere else in the state. It serves patients from every corner of the state, and is a conduit for learning for more than 3,400 students and trainees. OHSU is the source of more than 200 community outreach programs that bring health and education services to every county in the state.

As a leader in research, OHSU earned $307 million in research funding in fiscal year 2007. OHSU serves as a catalyst for the region's bioscience industry and is an incubator of discovery, averaging one new breakthrough or innovation every three days, with more than 4,100 research projects currently under way. OHSU disclosed 132 inventions in 2007 alone, and OHSU research resulted in 33 new spinoff companies since 2000, most of which are based in Oregon.