A new strategy for treating Alzheimer’s disease is in the works at Howard Hughes Medical Institute and Stanford University’s medical school.
Researchers led by Gerald Crabtree, MD, report their progress against Alzheimer’s disease (search) in the Oct. 29 issue of the journal Science.
Their approach does not cure the progressive brain disease, which affects memory, intelligence, language, judgment, and behavior, most often in older adults. Instead, it works to counteract the buildup of abnormal proteins called plaques (search) that clump and entangle in the brains of Alzheimer’s disease patients. The treatment could complement other Alzheimer’s disease treatments in development.
Up to 4 million Americans have Alzheimer’s disease, according to the Alzheimer’s Disease Education and Referral Center. The risk of developing Alzheimer's disease increases with age.
Scientists aren’t sure exactly what causes the disease. However, they know that the plaques disrupt nerve cells in the brain.
For years, researchers have sought ways to counteract those plaques. They’ve worked on developing molecules to unravel the plaques, but the large plaques just push the tiny molecules out of the way or ensnare them in their surface, rendering the molecules helpless in fighting Alzheimer’s disease.
Crabtree and colleagues took a different approach.
They designed a molecule that was small enough to slip into the cell and smart enough not to launch itself against the plaques.
Once inside the cell, the molecule attracts and binds onto a “chaperone” protein, a bulky but harmless protein that’s present in plentiful numbers and unrelated to Alzheimer’s disease. Held in place by its chaperone, the molecule also latches onto the abnormal proteins and prevents them from aggregating into plaques.
Crabtree’s team tried this so-called “Trojan horse” strategy in test tube experiments, which went well. The next step would involve experiments with mice.
If the idea works out, it might also work to sabotage proteins in troublesome organisms like HIV, the virus that causes AIDS, according to a Stanford news release.
SOURCES: Gestwicki, J. Science, Oct. 29, 2004; vol 306: pp 865-869. News release, Stanford University. WebMD Medical Reference from Healthwise: “Alzheimer’s Disease: Topic Overview.” WebMD Medical Reference from Healthwise; “Alzheimer’s Disease: What Happens.” WebMD Medical Reference from Healthwise: “What Increases Your Risk.” Alzheimer’s Disease Education and Referral Center.