Novel Medication May Block Progression Of Alzheimer's Disease

Ruzanna Harutyunyan's picture

Researchers at the University of Pennsylvania School of Medicine are conducting studies on an experimental medication to block nerve damage and inflammation in the brain that can lead to progressive memory loss and behavioral changes in people with Alzheimer’s disease. Current Alzheimer’s disease therapies focus on improving symptoms rather than attacking the root of the disease progression.

The buildup of plaques can trigger inflammation in the brains of people with Alzheimer’s disease (AD). A protein called amyloid beta builds up in plaque deposits and may promote damage to nerve cells. Researchers across the country will test an experimental drug that seeks to stop amyloid beta from binding to a particular receptor in the brain. This receptor, called RAGE, (receptor for advanced glycation endproducts), is believed to prompt an inflammatory reaction and has been linked to several chronic diseases, including Alzheimer’s and diabetes. Douglas Galasko, M.D., Professor of Neurology at the University of California, San Diego (UCSD), is directing the study.

“The evidence from basic research studies is compelling and merits further evaluation in a rigorous human clinical trial,” Galasko said. “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 study will recruit the 400 volunteers aged 50 and up at 40 sites nationwide, including the University of Pennsylvania School of Medicine. 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.


“In addition to monitoring disease progression through cognitive tests, we will examine various biological markers of the disease,” said Jason Karlawish, M.D., local principal investigator and Associate Director of the Memory Disorders Clinic at the University of Pennsylvania. “These include the degree of atrophy (or shrinkage) of the brain as measured by magnetic resonance imaging (MRI), the extent of amyloid buildup in the brain assessed by Positron Emission Tomography (PET) imaging, and levels of amyloid beta and other proteins in blood and spinal fluid.”

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 and who is getting the placebo.

The industry-sponsored study is being conducted by the Alzheimer’s Disease Cooperative Study (ADCS), a consortium of leading researchers supported by the National Institute on Aging (NIA), part of National Institutes of Health (NIH). The ADCS at UCSD will coordinate the 18-month, double-blind, placebo-controlled clinical trial. 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.