Alzheimer's disease vaccine a step nearer?
a vaccine against Alzheimer's disease, overcoming the side effects
that held back a prior vaccine for the disease.
The research also reveals that it can be possible to customise the response of the immune system with unprecedented precision.
Using a harmless version of the Herpes simplex virus, scientists at the University of Rochester Medical Centre put into mice a payload of genetic material designed to stimulate specific elements of the host immune response - and cut out the toxic side effects seen in a previous study in people of a vaccine against Alzheimer's developed by Elan and Wyeth.
Though the current study was not in people but in mice, researchers are excited because it demonstrates a level of control over an Alzheimer's vaccine that was previously unattainable. The work was published on-line in Neurobiology of Aging.
In 2002, Elan and Wyeth pulled the plug on their vaccine candidate, called AN-1972/ AIP-001, after 15 patients out of 360 were treated with the product experienced severe inflammation in the central nervous system that appeared to be directly linked to the vaccine.
With funding from the US National Institutes of Health, Howard Federoff and William Bowers of the Centre for Aging and Developmental Biology at Rochester, set out to create a vaccine without the harmful side effects.
As with the earlier vaccine, the aim was to develop a product that mounted an immune response against beta amyloid, a constituent of the plaques that characterise the brains of people with Alzheimer's. However, modified the immune response by combining it with tetanus toxin.
While the unmodified vaccine proved lethal to four out of six mice, the one coupled to a tetanus toxin proved much safer while still causing a 20 per cent decline in the amount of amyloid plaque in the brain.
"It appears that you need to induce specific immune activity to clear existing plaque or prevent the formation of new plaque deposits," said Bowers. "The herpes vector system gives us the flexibility to fine-tune the nature of the immune response so we can possibly create an effective vaccine that has a more optimal safety profile."
The team is conducting several more studies designed to contribute toward a custom vaccine against Alzheimer's. In addition, Bowers has just been awarded a five-year, $1 million grant from the NIH to study a closely related topic, the role of inflammation in the disease.
