Doctors at Emory University will begin testing a vaccine designed to slow the accumulation of amyloid plaques in the brains of patients with Alzheimer's disease.
Alzheimer's affects more than 4.5 million Americans and is marked by gradual nerve cell death and a progressive loss of memory and mental functioning. All of the medications now available aim to improve the functioning of the nerve cells that remain alive.
Several still-experimental vaccines or immunotherapies take a different approach. They target beta-amyloid, a naturally occurring protein that clumps together and forms plaques in the brains of Alzheimer's patients. The clumps appear to damage brain cells.
The study's main purpose is to evaluate the vaccine's safety, possible side effects and how well it stimulates the immune system.
"This is an exciting time for those who treat and care for people with Alzheimer's," says Allan Levey, MD, the principal investigator for the study and chairman of the Department of Neurology at Emory University School of Medicine. "By harnessing the patient's own immune system, it may be possible to change the course of the disease, rather than simply treat its symptoms."
Previous research on mice genetically engineered to develop an Alzheimer's-like condition has found that vaccination with beta-amyloid at birth protects them from plaque formation and mental decline. Older mice also showed some benefit from vaccination.
"Experiments in mice and still-limited evidence from human trials suggest that antibodies against the beta-amyloid protein can aid in clearing its buildup from the brain," Dr. Levey says.
An earlier clinical trial of a beta-amyloid vaccine in humans was halted in 2002 because a small fraction -- six percent -- of the participating patients developed meningoencephalitis, an inflammation of the brain and the tissue surrounding it.
The new vaccine, developed by the pharmaceutical firm Merck, uses a smaller piece of the beta-amyloid protein. The smaller piece is expected to stimulate antibody production but avoid activating T cells, which are the shock troops in an inflammatory response. This trial is the first time this vaccine will be used in people.
Despite the unacceptable safety profile of the previous vaccine, patients who developed antibodies against amyloid protein -- about 20 percent of those participating -- did appear to benefit.
As a group, "antibody responders" showed improvement on a set of tests designed to measure memory, decision-making and verbal ability, but not on other tests often used on patients with Alzheimer's, according to a 2005 study published in the journal Neurology.
Some antibody responders also showed reductions in the level of another protein called tau in their cerebrospinal fluid. Tau tends to build up inside neurons in Alzheimer's disease and scientists believe its presence in cerebrospinal fluid is related to cell death.
Other companies are testing related medications called passive immunotherapies, where a vaccine is replaced with pre-made antibodies either from human donors or engineered to resemble human antibodies. Emory researchers anticipate they will participate in these clinical trials later in 2008.
In the current study, sponsored by Merck, men and women ages 55 and older with mild to moderate Alzheimer's disease are eligible to participate. Several other medical centers across the United States and Sweden are also taking part.
The patient must have a reliable caregiver, who will attend all visits and answer questions about him or her. In addition, a patient must not live in a nursing home or facility, have another neurological disorder, have a history of stroke, drug or alcohol abuse, or have received blood donations or blood derived-products in the last six months.
"It is important for patients and caregivers to recognize that this is an experimental vaccine and some previous trials did fail," says Dr. Levey. "We can proceed only with a sense of balance and respect for patient safety."
Patients will receive three intramuscular injections of the vaccine or a placebo over the course of six months.
They will be monitored by magnetic resonance imaging (MRI) before each dose of vaccine to guard against indications of inflammation or other side effects. The study is expected to last for a total of four years.
For more information, call the Emory Alzheimer's Disease Research Center at 404-728-6950.
References: Gilman et al (2005), Neurology 64: 1553 / Schenk et al (1999), Nature 400: 173