UW testing new medicines in Alzheimer's fight

University of Washington scientists have begun testing two new drugs they hope will ease the symptoms and possibly prolong the useful lives of Alzheimer's disease patients, a group that is destined to grow by multitudes in the decades to come.

Researchers hope the drugs, which take a new approach to the disease, will do a better job than the current generation of medications that slow progression for only a few years.

"Right now in Alzheimer's disease, these [two new] drugs are the great hope," said Dr. Elaine Peskind, associate director of the UW Alzheimer's Disease Research Center at the VA Puget Sound Health Care System in Seattle.

One of the new medications seeks to remove the brain-altering plaque that partially causes Alzheimer's; the other is designed to prevent its production, Peskind said.

Scientists at the UW and dozens of other research centers are scrambling to make faster headway against the complicated disease in the face of anticipated record growth in the number of patients. An estimated 4.5 million U.S. residents now have Alzheimer's. The number is expected to increase to as many as 16 million by the year 2050, according to researchers at Rush University Medical Center, Chicago.

Peskind; Dr. Murray Raskind, director of the Alzheimer's Research Center; and their colleagues are testing the two new drugs in patient trials that primarily assess their human safety and look for hints of effectiveness that have been seen in lab animals. Patients with mild to moderate symptoms are enrolled in the trials.

To participate in drug trial

Patients with mild to moderate Alzheimer's disease symptoms may volunteer for the University of Washington trials of two experimental drugs. Call 206-764-2069 or 800-317-5382.

Other Alzheimer's research

Scientists also are investigating other means to thwart Alzheimer's disease. Some of these are:

Nonsteroidal anti-inflammatory drugs (NSAIDS): These include ibuprofen and some prescription drugs. Some studies have shown they lower the risk of Alzheimer's, possibly by reducing brain inflammation associated with the disease. Other research has shown they have no effect.

Cholesterol-lowering drugs (statins): The same drugs that help prevent heart disease may also lower the risk of Alzheimer's, some studies have suggested. Elevated cholesterol may be involved in the formation of plaque that clogs patients' brains. Other research, including one University of Washington study, suggests statins don't lower the risk.

Antioxidants: Some studies have suggested that antioxidants such as vitamins C and E may prevent naturally occurring brain-cell damage that increases with aging and could be a factor in Alzheimer's. Again, research findings conflict on whether there are benefits. A UW study is looking at whether a combination of antioxidants may be more effective than just one.

Targeting protein

One of the drugs, sponsored by the biotech company Élan, of Dublin, Ireland, is targeted at beta-amyloid, a protein that forms a plaque. The plaque clogs spaces between brain cells, disturbing electrical impulses between the cells and impairing memory, reason and the ability to move and speak.

The drug, for now called AAB-001, uses monoclonal antibodies produced in the lab in hamster cells and sensitized only to beta-amyloid. After they are injected into the body, the antibodies bind only to beta-amyloid and remove it from the brain. The trial involves 240 patients, aged 50 to 85, in 30 medical centers across the country and will last 2 ˝ years. UW researchers already have seven participants and are seeking several more.

Raskind said tests so far have found no serious side effects. He said small, temporary changes in MRI images of the brain were found in several patients, but only one had a symptom — temporary dizziness. If the drug proves safe and likely effective, it will move on to a large-scale tests of its effectiveness.

Researchers are especially wary of side effects of any drugs after tests of an experimental Alzheimer's vaccine made by Élan eliminated plaque but caused dangerous brain inflammation in 15 patients. The vaccine, which used the immune system to fight the plaque, was withdrawn from trials four years ago. Monoclonal antibodies used in the new drug do not involve the immune system, Peskind said.

Blocks enzyme

The second drug being tested at the UW is made by Eli Lilly and is designed to prevent production of beta-amyloid. The drug blocks an enzyme, gamma secretase, needed by the body to make beta-amyloid.

Five other medical centers besides the UW are participating in the trial, which will last an additional nine months. The UW has 13 participants and is seeking more.

The drug, temporarily called LY450139, is taken twice a day as a pill. It has caused diarrhea and nausea in some patients.

Four prescription drugs for patients with mild to moderate Alzheimer's symptoms already are on the market. All increase the amount of a brain chemical, acetylcholine, used by cells to transmit electrical impulses to one another. All slow symptoms for a few years, but patients don't get much better, Peskind said.

Another drug normalizes the action of glutamate, another nerve-impulse transmitter that is overactive in Alzheimer's patients.

The two new drugs being tested at the UW are not viewed as cures. The best hope is that they might stop progression of Alzheimer's or slow it long enough for patients to live out a normal lifespan, Peskind said.

"We need the cure," she said. "This is a looming public-health crisis."

Warren King: 206-464-2247 or wking@seattletimes.com