17th January 2013

Major step toward an Alzheimer's vaccine

A team of researchers from Université Laval, CHU de Québec, and pharmaceutical firm GlaxoSmithKline (GSK) has discovered a way to stimulate the brain's natural defence mechanisms in people with Alzheimer's disease.

This major breakthrough – published in the 15th January early edition of PNAS – opens the door to a new treatment for Alzheimer's disease and a vaccine to prevent the illness.

One of the main characteristics of Alzheimer's is the production in the brain of a toxic molecule known as amyloid beta. Microglial cells, the nervous system's defenders, are unable to eliminate this substance, which forms deposits called senile plaques (illustrated above).

The team led by Dr. Serge Rivest identified a molecule that stimulates activity of the brain's immune cells. The molecule, known as MPL (monophosphoryl lipid A), has been used extensively as a vaccine adjuvant by GSK for many years, and its safety is already well established.

In mice with Alzheimer's symptoms, weekly injections of MPL over a 12-week period eliminated up to 80% of senile plaques. In addition, tests measuring the mice's ability to learn new tasks showed significant improvement in cognitive function over the same period.

The researchers see two potential uses for MPL in humans. It could be administered by intramuscular injection, to slow the progression of the illness. It could also be incorporated into a vaccine designed to stimulate the production of antibodies against amyloid beta.

"The vaccine could be given to people who already have the disease to stimulate their natural immunity," said Dr. Rivest. "It could also be administered as a preventive measure to people with risk factors for Alzheimer's disease."

With an 80% reduction in protein deposits, this method is even more successful than another breakthrough which was reported last year, in which turning off cytokines (immune system signal transmitters) reduced plaques in mice by 65%. How well this translates into humans, of course, remains to be seen.

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