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May 09, 2013
 |  BC Innovations  |  Targets & Mechanisms

AD vaccine redux

Researchers at Harvard Medical School have teamed up with vaccine maker Mercia Pharma Inc. to design a next-generation Alzheimer's disease vaccine with an adjuvant that promotes a beneficial anti-inflammatory

response that the team hopes will enhance b-amyloid clearance without triggering neuroinflammation.1

AD is caused by accumulation of b-amyloid (Ab), an extracellular protein fragment that forms deposits around neurons. Those deposits, or plaques, trigger neuronal degeneration and attract inflammatory microglia, which further accelerate neuron death. Preventing the formation of Ab plaques or clearing away Ab before it reaches toxic levels is the central focus of AD therapeutic development.

In principle, Ab can be targeted with injected antibodies, but this passive immunotherapy approach has thus far met with failure. Two Ab-binding mAbs-bapineuzumab (AAB-001) from Johnson & Johnson and Pfizer Inc. and solanezumab (LY2062430) from Eli Lilly and Co.-failed in Phase III testing to prevent AD progression in patients with mild to moderate disease.

The most recent casualty is Gammagard Liquid 10%, a polyclonal mixture of antibodies from Baxter International Inc. that failed in a Phase III trial in a population of patients with mild to moderate AD.

An alternative approach consists of building up a patient's natural immune response against Ab before the onset of disease. The simplest way to do so is with active immunotherapy or vaccination, in which Ab is introduced to the peripheral immune system in a nontoxic form that stimulates a robust antibody-based response.

This was the idea behind the AN-1792 AD vaccine candidate from Elan Corp. plc and Wyeth (now Pfizer). However, that product failed to prevent AD progression in Phase II testing in 2002, partly because of a poor antibody response in...

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