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

Final Report Summary - MIMOVAX (Alzheimer's disease-treatment targeting truncated Aß40/42 by active immunisation)

Alzheimer's disease (AD) is the most common form of dementia in humans and is caused by the abnormal deposition of Beta-amyloide (BA) plaques associated with extensive neuronal loss in the brain of patients. At present, no effective treatment is available to stop the progressive neuro-degeneration and associated cognitive decline in AD patients.

The MIMOVAX project was a Specific Targeted Research Project (STREP) for the development and optimisation of a novel treatment to stop the progression of AD. Thus, the goal of the project was the development of a safe and efficacious AD vaccine against modified forms of BA, which was predicted to avoid the development of immunological complications due to autoreactive T-cells. The immune system of AD patients would be activated to attack and remove BA and therefore directly fight the cause of the disease. Therefore, the development of such innovative AD vaccines targeting truncated and modified forms of Aß would be a safe treatment regimen to efficiently fight AD in patients and would limit the severe personal and economic impacts of AD on patients, their families and society.

The novel technology that was presented by the project was developed to create antigens mimicking the structure of neo-epitopes which did not contain sequences of the native Aß peptide. A mimotope-based AD vaccine induced antibody responses exclusively reacting with the pathological truncated and modified forms of the Aß molecules but not with parental structures like the Amyloid precursor protein (APP).

The first step in MIMOVAX was the identification and evaluation of novel mimotopes mimicking epitopes present on different Aß derivatives. Subsequently, these novel vaccine candidates were tested for efficacy of altering disease progression in animal models. The evaluation included the analysis of AD pathology in the brain, as well as the testing of memory and learning in the animals by cognitive tests in vivo. The successful candidate was then tested for tolerability and safety in a clinical trial in AD patients. In addition, new diagnostic methods were proposed in order to monitor treatment efficacy in vivo in animal models and to foster the development of novel tracers for diagnosis and monitoring of AD in patients.

During the first reporting period the consortium identified novel monoclonal antibodies and their respective affitopes. Within the second reporting period it was demonstrated that the innovative MIMOVAX AD vaccine was able to reduce amyloid plaque load and alleviate the pathologic hallmarks in the brain of animal models for AD. In addition, improved spatial memory and learning in transgenic animals was observed. The project team also demonstrated the safety of the vaccine stability by extensive testing and by toxicological analyses in animals. During the third reporting period the preparation of documents for the application of the clinical trial was initiated and the first active trials for the evaluation of safety and tolerability of the vaccine were performed.

The obtained results were disseminated to the scientific community and the general public through various pathways. Firstly, a project website was launched and regularly updated with MIMOVAX information. Secondly, conventional media coverage was planned to complement the public access website. Moreover, the scientific community was informed via peer reviewed publications and presentations at international conferences.

The expected end result of the MIMOVAX project, which would be achieved beyond the project time frame, was the demonstration of safety of the innovative vaccine targeting Aß in patients suffering from AD. The finalised proposal could assist in the development of a safe treatment regimen in further clinical testing.

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