Potential Alzheimer's Vaccine Shows Early Promise

Jeannette Y. Wick, RPh, MBA, FASCP
Published Online: Wednesday, February 6, 2013
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Regular injections of monophosphoryl lipid A, a vaccine adjuvant, reduced cerebral amyloid beta in a mouse model of Alzheimer’s disease by up to 80%.

Researchers from Laval University, CHU de Quebec, and GlaxoSmithKline (GSK) have reported progress in their quest for a vaccine to prevent Alzheimer’s disease (AD). Using a mouse model of AD, they have successfully stimulated the brain’s natural defense mechanisms with monophosphoryl lipid A (MPL), a vaccine adjuvant that has been used extensively by GSK.
 
Recently, researchers have noted that AD is probably caused by an inability to clear amyloid beta, as opposed to increased amyloid beta production. In AD patients, microglial cells that normally clear foreign matter are unable to eliminate amyloid beta, allowing deposits to build up and create senile plaques. Accumulating amyloid beta keeps the microglial cells activated, however, which may trigger the release of exaggerated cytokines and neurotoxic mediators, causing harm to neurons.
 
In their study, published in the January 29, 2013, issue of the Proceedings of the National Academy of Sciences, the researchers gave the mice weekly MPL injections for 12 weeks. The researchers report that this resulted in a reduction of cerebral amyloid beta load by up to 80%. In addition, the mice demonstrated significant improvement in cognitive ability.
 
GSK has considerable experience with MPL, which is a Toll-like receptor 4 agonist, and its safety is well-established. Agents that promote amyloid beta elimination by scavenger cells (monocytes, macrophages, or microglia), as MPL appears to do, could potentially be used to prevent or treat AD in patients at high risk. In patients already diagnosed with AD, this type of therapy might slow disease progression. As a vaccine component, it might stimulate antibody production against amyloid beta.

Ms. Wick is a visiting professor at the University of Connecticut School of Pharmacy and a freelance writer from Virginia.

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