Vaccination against Alzheimer’s? We could be one step closer.


It’s always good to hear encouraging news, especially when it is about a potential treatment for Alzheimer’s disease. A recent report on the evening news spoke about a vaccine being developed through the University of Sydney.

Associate Professor Lars Ittner from Sydney’s Brain and Mind Research Institute is leading a study into developing a vaccine that targets a specific brain protein called tau that is associated with Alzheimer’s disease and fronto- temporal dementia.

In people with dementia, the tau protein forms what are called neurofibrillary tangles, which leads to neuronal death and loss of brain function.

In this study on mice, the vaccine was shown to slow down the development of further neurofibrillary tangles. There was no effect on those tangles that had already formed. So the prospect is that it might be possible if future development of this vaccine occurs for this to be be used in humans once the diagnosis of dementia has been made, and slow down progression of the disease. It is not a cure, but it could buy the person more time for cognitive functioning and possibly work as a preventative if someone is perceived to be at higher risk of developing dementia.

Other researchers around the world have also been looking to develop a vaccine, one to either target tau or amyloid.

Professor Ittner commented that in many studies, vaccines were being trialled in mice with dementia, prior to the onset of clinical symptoms. This study is the first to show that a vaccine targeting tau can be effective once the disease has set in. It is known that the pathological changes associated with Alzheimer’s disease start many years before the clinical onset of symptoms. Having a treatment to slow down further progression would be huge step in the right direction.

Earlier this year I wrote a blog about a nasal spray being developed to minimise the potential risk of vascular dementia.

Researchers at Georgetown University, Washington D.C have found that if an antibody is given later in the progression of Alzheimer’s the greater the chance that it will trigger brain inflammation.

In their studies, mice with Alzheimer’s symptoms were given an antibody called PFA1, which was designed to clear amyloid from their brains. Those mice with the greatest amount of amyloid present at the beginning of treatment showed a greater inflammatory response. The take home from this was that the greatest benefit to lower the amount of amyloid would be obtained by using it early on i.e. in the early stages of the disease.

In Germany, researchers at the University of Rostock are investigating a protein ABCC1, which has been shown to help remove amyloid from mice brains. They have also been using a drug commonly used for treating nausea and vomiting (thiethylperazine) to activate this protein, suggesting that using this drug could be of potential benefit to prevent the development of amyloid plaques.

In the US, Scott Webster at the Georgia Health Sciences University in Augusta is also working on an Alzheimer’s vaccine. His vaccine is targeted versus two brain proteins: amyloid and RAGE (receptor for advanced glycation end-products). The RAGE protein helps the amyloid get into the brain and contributes to the inflammatory process that the amyloid causes to the brain’s neurons.

Webster’s vaccine is different in that it targets these two proteins. The vaccine uses the body’s own immune system to protect against the overproduction of RAGE and amyloid. His vaccine is different also in that it can be taken orally thus using the gut’s bacteria which are vital to our immune system. Previous vaccines developed elsewhere that have targeted just amyloid, have failed to show benefit in clinical trails and some have also had significant side effects. By targeting the two proteins, Webster is more hopeful that this combination effect will lead to reducing or eliminating the toxic effects of the brain inflammation. Early results in animal studies have been encouraging so far, so the next step will be to use the vaccine trialled in larger animal studies.

With all this amazing work going on around the world we are surely moving closer to having more effective treatments that will be able to stop Alzheimer’s in it’s tracks.

Refs:

Bi M, Ittner A, Ke YD, Götz J, Ittner LM (2011) Tau-Targeted Immunization Impedes Progression of Neurofibrillary Histopathology in Aged P301L Tau Transgenic Mice. PLoS ONE 6(12): e26860. doi:10.1371/journal.pone.0026860

American Friends of Tel Aviv University (2011, February 28). An Alzheimer’s vaccine in a nasal spray?. ScienceDaily. Retrieved December 10, 2011, from http://www.sciencedaily.com¬ /releases/2011/02/110228104310.htm

Markus Krohn, Cathleen Lange, Jacqueline Hofrichter, Katja Scheffler, Jan Stenzel, Johannes Steffen, Toni Schumacher, Thomas Brüning, Anne-Sophie Plath, Franziska Alfen, Anke Schmidt, Felix Winter, Katja Rateitschak, Andreas Wree, Jörg Gsponer, Lary C. Walker, Jens Pahnke. Cerebral amyloid-β proteostasis is regulated by the membrane transport protein ABCC1 in mice. Journal of Clinical Investigation, 2011; DOI: 10.1172/JCI57867

Georgia Health Sciences University (2011, September 26). Research points new way to possible Alzheimer’s vaccine. ScienceDaily. Retrieved December 10, 2011, from http://www.sciencedaily.com¬ /releases/2011/09/110926104609.htm

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