Vaccines - Alzheimer's Disease

There are a number of promising vaccines currently being developed for the treatment of Alzheimer's disease.

Alzheimer's disease is associated with the build up of beta-amyloid plaques that cause the degradation of nerve cells. Most treatments are aimed at preventing the formation of plaques, or breaking up plaques that already exist.

AFFiRiS AG is an Austrian company that has recently entered its Alzhemier's vaccine, AD02, into phase II trials.¹ This means that the vaccine will be used on a large group of human volunteers, as previous small-scale trials have shown positive results. AD02 works by identifying and attacking Alzheimer-related beta-amyloid plaques, and breaking them up.

A group in India has developed an alternative vaccine which they claim is safer than current vaccines,² as it is based on a synthetic form of beta-amyloid, while antibodies can still identify it, and prevent the build up of plaques.

A large collaborative research group in Ohio, USA, has studied the usage of a specific peptide both before the onset of Alzheimer's disease, and after.³ The peptide is similar to a specific part of the plaque-forming beta-amyloid, and therefore induces the immune system to make antibodies specific to these proteins. The group suggests that this peptide provides a much safer alternative to current vaccination strategies.

The usage of DNA in a vaccine that might prevent and treat Alzheimer's disease has also been investigated.⁴ Researchers at the University of Texas studied the effect of vaccinating mice with DNA. The DNA causes the production of beta-amyloid in the mouse which triggers the mouse's immune response against the Alzheimer-causing forms of beta-amyloid. Therefore these mice would have better defence against the onset of Alzheimer's disease, since their immune systems will have been primed against it.

And finally, a totally different approach has been taken by the group of Tsuneya Ikezu at the University of Nebraska. Instead of using beta-amyloid in a vaccine, they've studied the usage of a signalling molecule that plays an important role in controlling inflammation.⁵ This molecule, interleukin 4, plays an important role in immune response. In mice models it was shown that increased levels of interleukin 4 was associated with a decrease in beta-amyloid plaque formation and an increase in nerve cell growth. It also improved spatial learning, showing that it supports brain function.


¹ Press release from AFFiRiS AG
Source

² Subramanian S et al. Design and development of non-fibrillar amyloid β as a potential Alzheimer vaccine. Biochemical and Biophysical Research Communications 394: 393-397 (2010).
Source

³ Wang CM et al. Immunization with the SDPM1 peptide lowers amyloid plaque burden and improves cognitive function in the APPswePSEN1(A246E) transgenic mouse model of Alzheimer's disease. Neurobiology of Disease 39: 409-422 (2010).
Source

⁴ Qu BX et al. Analysis of three plasmid systems for use in DNA Aβ42 immunization as therapy for Alzheimer's disease. Vaccine 28: 5280-5287 (2010).
Source

⁵ Kiyota T et al. CNS expression of anti-inflammatory cytokine interleukin-4 attenuates Alzheimer’s disease-like pathogenesis in APP+PS1 bigenic mice. doi: 10.1096/fj.10-155317 (2010).
Source