Renewed Hopes for Vaccine to Treat Alzheimer's

June 13, 2006

In 2003 preliminary clinical trials of a vaccine to treat Alzheimer's disease were halted because 18 of the 298 patients developed swelling in their brains. The doctors had hoped that by exposing the human immune system to small amounts of beta-amyloid--a protein thought to initiate the buildup of plaques in the brain that underlies the neurodegenerative disease--it could be trained to expel the rogue protein. Instead, in 6 percent of the patients, the immune system overreacted and damaged the brain itself. Now scientists have developed a new DNA-based vaccine that causes cells to produce extra beta-amyloid, thereby engaging the immune system to attack the protein. Plus, when administered to mice, it had no adverse effects. Yoh Matsumoto of the Tokyo Metropolitan Institute for Neuroscience and his colleagues developed the vaccine by tinkering with the DNA that governs beta-amyloid production. The researchers then tested the vaccine under two conditions: as a preventative against development of plaques and as a therapy once plaques had developed. This meant vaccinating specially bred mice from the age of three months--before they had developed plaques--and after 12 months--once plaque cluttering had begun.

After just four months of biweekly injections, mice in the preventative group had as much as 30 percent less beta-amyloid buildup than untreated controls had; after a year, up to 50 percent less. "The final reduction rate of beta amyloid burden in the cerebral cortex at 18 months of age was roughly 38.5 percent of untreated groups," the team writes in their report, published online this week by the Proceedings of the National Academy of Sciences. The DNA vaccine was also effective as a therapy. After just six months of treatment, it cut beta-amyloid levels by as much as 40 percent. Most importantly, no matter how often the vaccine was administered, no brain swelling was observed. "Nonviral beta-amyloid DNA vaccines are highly effective and safe in reducing the beta-amyloid burden in model mice and, thus, are promising as a vaccine therapy against human Alzheimer's disease," the researchers conclude. --David Biello