Alzheimer's disease-treatment targeting truncated Aß40/42 by active immunisation

Objective

Alzheimer's disease (AD) is the most common form of dementia in humans. According to the Alzheimer Association there are currently 12 million patients worldwide with estimated social costs for every patient reaching 40,000 per year. At present, no effective treatment is available to stop the progressive neuro-degeneration and associated cognitive decline in AD patients. AD is characterized by the abnormal accumulation of amyloid plaques in the brain.

These plaques mainly consist of the Amyloid-(A) peptides Aß40/42 derived from the Amyloid Precursor Protein (APP). Immunotherapeutic treatment targeting Aß led to amyloid plaque reduction and had beneficial impact on disease progression in animal models. However, the first phase II clinical vaccination trial in AD patients using full length Aß42 as antigen had to be discontinued due to severe neuroinflammatory side effects including brain infiltration by autoreactive T-cells. In humans most of the amyloid plaque material is formed by N-terminally truncated and modified Aß derivatives. These truncated Aß species are correlated with increasing severity and early onset of neurodegeneration in AD patients.

In light of the characteristics of amyloid composition in patients, these truncated Aß peptides are highly attractive targets providing neoepitopes not present on parental APP. The Mimotope technology presented in this proposal will be used to create antigens mimicking potentially pathological B-cell epitopes on truncated Aß. A Mimotope-based AD vaccine targeting truncated forms of Aß would therefore induce a safe antibody response exclusively reacting with the pathological Aß molecules but not with parental APP and would avoid the induction of autoreactive T-cells. Thus the MimoVax vaccine will provide an innovative, safe, cost effective and efficient approach to successfully treat AD patients and to limit the severe personal and economic impact of AD on patients, their families and society.

Fields of science

• natural sciencesbiological sciencesneurobiology
• medical and health sciencesbasic medicineneurologydementiaalzheimer
• medical and health sciencesbasic medicineimmunologyimmunisation
• medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccines
• medical and health sciencesbasic medicinepathology

Programme(s)

• FP6-LIFESCIHEALTH - Life sciences, genomics and biotechnology for health: Thematic Priority 1 under the Focusing and Integrating Community Research programme 2002-2006.

Topic(s)

• LSH-2005-1.2.4-7 - Development and testing of new preventive and therapeutic tools, such as somatic gene and cell therapies (in particular stem cell therapies, for example those on neurological and neuromuscular disorders) and immunotherapies

Call for proposal

FP6-2005-LIFESCIHEALTH-7
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Funding Scheme

Coordinator

Participants (10)