A DNA vaccine has successfully reduced the symptoms of Alzheimer's disease in mice. The result could signal the first preventative and restorative treatment vaccine for Alzheimer’s without serious side effects.
Alzheimer’s disease progresses as small proteins called amyloid beta (Ab) peptides are overproduced, forming plaques in the brain that interfere with its function. Memory loss and mental deterioration follow.
A vaccination approach – getting the immune system to clean up the plaques – has been considered the most promising way to tackle the disease, but its success has been limited, until now. In 2002, for example, the US pharmaceutical company Elan halted trials of a vaccine that raised antibodies against Ab peptides, after some patients suffered brain inflammation (see Key Alzheimer's vaccine trial abandoned).
The new vaccine is different because instead of using the Ab peptide itself to stimulate antibody production, it uses a stretch of DNA that codes for the Ab peptide, says Yoh Matsumoto, at the Tokyo Metropolitan Institute for Neuroscience, Japan, who led the research.
Into the brain
Since DNA vaccination stimulates the immune system more gently than peptide vaccination, it should also avoid the brain swelling seen in the Elan trial.
The researchers use mice engineered to develop Alzheimer’s-like symptoms by producing Ab peptides in the brain, which in turn form the plaques that lead to cognitive impairment.
Matusmoto’s team injected the mice with the DNA vaccine before Ab peptides had started to build up. The DNA is read by the muscle cells into which it is injected, and Ab peptide is produced. Antibodies to it are then raised by the immune system and cross into the brain.
Mice treated preventatively, at 7 or 18 months of age, developed 15.5% or 38.5% fewer Ab peptides, respectively, than did untreated mice. This suggests that the vaccine was having a protective effect on the mice.
Human trials
When the DNA vaccine was used as a treatment in mice that had already started producing the Ab peptides, their Ab peptide burden was reduced by about 50%. “Ab peptide reduction to 50% that of unvaccinated mice is sufficient [for the return of normal cognitive function]," says Matsumoto.
If these results are replicated in monkeys, he hopes that clinical trials in humans could start within 3 years.Nick Fox, of the Institute of Neurology at University College, London, UK, says that DNA vaccination is an extremely promising way of slowing the progression of Alzheimer’s. “The key will be what happens in humans,” he says.
Journal reference: Proceedings of the National Academy of Sciences (vol 103, p 9619)
My Mother's half sister and my Great Grandfather died from complications of Alzheimer's and in reading my Grandmother's journal about her father's last years, it was a terrible time for the family. He was a doctor who at the young age of 58 began to show signs of dementia. With my Aunt, she was in her early sixties when her "forgetfulness" began to be noticed as something more than the ordinary. The last time I saw my Aunt, she was curled up in a fetal position on a hospital bed in a nursing home, totally unresponsive. Those images are forever burned into my mind. So, a scientific breakthrough in this disease would be very welcome.
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