Tau-based vaccines as a novel tool for Alzheimer’s Disease treatment

Alzheimer’s disease (AD) is a neurodegenerative disorder that is caused by conformational change of a normal β-amyloid peptide into oligomeric form. These fibrillary peptides become deposited in the brain in form of plaques, which are said to be the most toxic for neural cells. Additionally, abnormally phosphorylated protein, called Tau, accumulates in form of neurofibrillary tangles that are considered as a second major triggering factor of the pathology.

Unfortunately, currently there is no cure for the disease and the treatment is focused rather on the relief of symptoms. Moreover, as the societies in developed countries become older and older, there is an emerging need of novel therapeutic approaches. One of them is the concept of immunotherapy, in other words, application of vaccines that may potentially efficiently slow down the progression of the disease.

Recently, numerous clinical trials have been performed in order to test the efficiency of immunotherapy against β-amyloid. Although early studies on mice were quiet promising, large-scale studies of vaccines targeting β-amyloid were rather unsuccessful with very minor or no cognitive improvements. Hence, scientists are now focusing their attention more towards immunotherapy with Tau protein as a target.

In 2014, an interesting research was published by Slovak scientists that immunized rats against Tau. It appeared that vaccination resulted in elimination of Tau aggregation and occurrence of neurofibrillary tangles. Such findings give hope that immunization approach is a potential candidate for AD treatment.

At the beginning of the same year, the Switzerland-based biopharmaceutical company, AC Immune, has started clinical trials involving application of AD vaccine candidate, ACL-35. ACL-35 is aimed to stimulate host immune system to produce antibodies against phosphorylated form of Tau proteins. Currently, the vaccine is in Phase IIb trials and is the first one directed against Tau.

However, whether the ACL-35 will successfully enter the market is not so certain as novel improved β-amyloid vaccines are going to be developed in the next few years. The positive thing is that there is a huge interest in AD therapies and the hope for the efficacious cure is now much stronger than it used to be.

Sources:

http://www.pharmavoice.com/newsreleases/tau-based-vaccines-transform-early-alzheimers-disease-treatment-says-globaldata-analyst/

http://www.futuremedicine.com/doi/abs/10.2217/imt.11.170?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed&

http://alzres.com/content/6/4/44

http://www.fiercevaccines.com/story/ac-immune-begins-first-trial-tau-targeting-alzheimers-vaccine/2014-01-13

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3026780/

Maciej Smolarz