New Weapons Against Alzheimer's Disease
Possible Use of Vaccines and Experimental Drugs Are Explored by Researchers

By Sally Squires, Washington Post

 July 18, 2000

Alzheimer's disease is feared by nearly everyone, and with rates projected to triple in the coming years, it's a diagnosis that increasing numbers will face. While there's still no cure and little understanding of its cause, new research findings presented last week at the World Alzheimer Congress 2000 herald some bold new approaches that could soon make a difference in treatment and prevention of this illness.

"This is a growing global crisis, and we need to attack this disease from all directions," said Bill Theis, vice president of medical and scientific affairs for the Alzheimer's Association.

From learning about the protective effects of eating an antioxidant rich diet to the dangers of high blood cholesterol to an experimental drug that may help regenerate brain cells, the latest scientific findings are giving researchers new possibilities to one day prevent and treat Alzheimer's disease.

"It's very promising," said Neil S. Buckholtz, chief of the National Institutes on Aging's Dementias of Aging Branch. "The increased rate of understanding the disease is translating into potential new therapies."

Among the most exciting is the development of a possible vaccine for Alzheimer's disease, widely reported on last week. Animal studies suggest that the vaccine, known as AN-1792, removes the tangled, amyloid brain plaques that are a hallmark of the illness. Researchers don't yet know whether the build-up of brain plaques helps cause symptoms or is a consequence of the disease, but they believe that eliminating the plaques could help fight the disease or relieve its symptoms.

"We developed a greater understanding of how the vaccine works to clear amyloid plaques out of the brain and prevent additional plaques from forming," said Dale Schenk, vice president of discovery research at Elan Pharmaceuticals.

At the World Alzheimer Congress, which ends today, Schenk reported that the vaccine was also safely tolerated by other species, including rabbits, guinea pigs and monkeys. It was so well tolerated, in fact, that the Food and Drug Administration gave Elan approval to test the vaccine in 100 people with mild to moderate Alzheimer's disease.

Two dozen patients in the United States have already received one dose of the vaccine with no ill effects, Schenk said. Eighty additional patients in England will soon receive multiple doses of AN-1792, which is a synthetic form of the naturally occurring beta-amyloid protein. In animals, the vaccine appears to prompt the body to produce tiny proteins that tag the amyloid for removal by special scavenger cells in the brain.

Whether AN-1792 will show similar results in people won't be known until many more studies are completed, and experts cautioned that promising trends in animal research do not always hold up in humans.

But scientists were also heartened by work conducted by an independent team of researchers from the University of Toronto. Led by Peter St. George-Hyslop and Christopher George Janos, the study confirmed Elan's results in a different strain of mice and showed for the first time that removal of the plaques can help to improve neurological function. Animals treated with the vaccine were better able to navigate a maze.

"This is the nearest thing we've got to something that might work," said Marcelle Morrison-Bogorad, associate director of the National Institute on Aging's Neuroscience and Neuropsychology of Aging Program.

Another development showing promise at the congress is an experimental drug called memantine, which acts on a key brain receptor and may help slow the progression of more advanced cases of Alzheimer's disease. Currently, only a few drugs are approved for treatingAlzheimer's disease. They work exclusively to increase levels of acteylcholine, a brain chemical that helps transmit nerve impulses. But they can have uncomfortable gastrointestinal side effects, such as nausea and diarrhea.

Memantine, which is already on the market in Germany as a treatment for dementia and organic brain problems and has been licensed in the United States to Forrester Pharmaceuticals, acts on the NMDA receptors in the brain. NMDA receptors regulate levels of glutamate, another key brain chemical. Reporting on the results of a study of 250 patients treated at 30 medical centers throughout the United States, New York University's Barry Reisberg said that memantine significantly slowed progression of symptoms in Alzheimer's patients and appeared to be free of side effects.

"This is exciting and encouraging on many fronts," Reisberg said.

The study is one of the few to show effects in those with more advanced symptoms. "We are pleased to see research that may lead to effective medications for people with moderately severe to severe Alzheimer's disease, since currently no treatment options have label indications for people in those stages," said Theis of the Alzheimer's Association.

Neotrophin, an experimental drug that seems to help boost nerve growth factors in the brain, is also showing promise for more advanced patients. Developed through an NIA small business grant to NeoTherapeutics of Irvine, Calif., the drug has already been proven safe in humans.

The latest studies of the drug, also presented at the World Alzheimer Congress, suggest that Neotrophin may help improve cognition in people with moderate symptoms. (Those with mild symptoms showed less improvement.) Nearly 400 patients were randomly assigned to receive either a placebo or Neotrophin in one of three doses. They took the drug, which is given in a liquid suspension, for 90 days. Patients receiving the drug showed a "positive trend in both cognitive and behavior measures" after a 28-day period, the researchers report. Longer-term use is still under study, and more trials are planned in the United States and overseas. But NeoTherapeutics officials are hopeful about longer-term results.

"One thing that became clear is that the improvement doesn't seem to peak in 90 days," said Michelle Glasky, vice president of scientific affairs for NeoTherapeutics. "It looks like for a drug such as Neotrophin that has nerve regeneration properties, that we will have to treat longer than 90 days to see the full regeneration."

To help answer that question, the company will soon begin a six-month international trial involving 1,500 patents.

The combination of these and other new therapies is what may finally help battle Alzheimer's disease. "All these are different approaches to different stages of Alzheimer's disease," NIA's Buckholtz said. "They are all complementary. At this time we really don't know what is going to work and what will not at the various stages of Alzheimer's disease, so we have to be very open to all the possibilities."

RESOURCES

More information on Alzheimer's disease is available from:

* The Alzheimer's Association, 919 North Michigan Ave., Suite 100, Chicago, IL 60611-1676. Phone 312-335-5813. www.alzheimer2000.org

* Alzheimer's Disease Education and Referral Center, National Institute on Aging, P.O. Box 8250, Silver Spring, MD 20907-8250. Phone: 800-438-4380. http://www.alzheimers.org/