TAMPA, Fla. -- A safe and effective vaccine against Alzheimer's disease seems to be back on track, this time by transdermal patch delivery, according to researchers here.
TAMPA, Fla., Jan. 23 -- A safe and effective vaccine against Alzheimer's disease may be back on track, this time by transdermal patch delivery, according to researchers here.
In experimental mice, transcutaneous vaccine administration with beta amyloid peptide sharply reduced the levels of beta amyloid proteins that muddy the brain in Alzheimer's, found Jun Tan, Ph.D., M.D., of the University of South Florida.
There was saw no sign of the worrisome side effects, including cerebral micro-hemorrhage and meningitis caused by T-cell infiltration, that had sidelined a human clinical trial of a similar vaccine delivered intraperitoneally, the researchers reported online in the Proceedings of the National Academy of Sciences.
The ability of a peptide vaccine to produce an immune response and clear deposits of beta amyloid has previously been demonstrated, Dr. Tan said. "This study is the first to demonstrate that immunization using the skin may be an effective way to reduce A? (beta amyloid peptide) pathology," he added.
Terrence Town, Ph.D., a co-author, added, "The beauty is that something as simple and non-invasive as a skin patch could potentially be a promising therapy for Alzheimer's disease."
The study was begun after a study of synthetic amyloid-beta in 360 volunteers led to 12 cases of meningitis, thought to be the result of activated T-cells against beta amyloid infiltrating the brain. The vaccine in that study was given intraperitoneally.
The researchers hypothesized that the Langerhans cells in the skin might help mediate the immune response and prevent the toxicity, Dr. Tan said.
For the study, experimental mice -- both wild-type and a strain prone to developing amyloid plaques -- had the vaccine painted on a shaved section of their backs.
The mice developed high levels of anti-amyloid antibodies, the researchers found, and the Langerhans cells near the shaved sections were positive for the amyloid protein, showing that they had been involved in the immune response.
The researchers also found -- in the mice that developed plaques -- that the levels of amyloid beta in the peripheral blood increased rapidly after immunization in association with reduced brain levels, suggesting that the proteins were being removed from the brain and distributed into the blood.
At 10 months of age, the animals showed reductions of about 50% in amyloid deposits in their hippocampal and cortical regions. Compared with non-immunized animals, the reductions were statistically significant at P<0.001.
"Together, these results demonstrate that (transcutaneous) immunization with (the vaccine) is effective in reducing cerebral amyloidosis," Dr. Tan and colleagues reported.
Moreover, they said, the animals showed no sign of infiltrating T-cells against beta amyloid in the brain tissue, although specific T-cell responses were seen in the peripheral blood.
There was also no sign of cerebral microhemorrhage, the researchers said.
The next step, Dr. Tan said, is to see if the transcutaneous vaccine can curb memory loss in the mice as well as reduce the amount of amyloid plaques.
"If those studies show clear cognitive benefits," Dr. Tan said, "we believe clinical trials to evaluate a beta amyloid skin patch or topical cream in patients with Alzheimer's would be warranted."