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R&D strategy

Misfolded proteins are leading causes of neurodegenerative diseases


The progression of neurodegenerative diseases, such as Azheimer’s and Parkinson’s disease are all associated with pathologies that involve misfolded proteins. Research has shown that misfolded proteins, such as Abeta, Tau and a-synuclein are unable to carry out their normal functions and aggregate to form certain types of deposits that damage brain tissue.


In today’s understanding, these misfolded proteins play a key role in the pathology of neurodegenerative diseases (see diagram below). Typically, protein misfolding occurs during cellular stress, which can be triggered by many different causes, including oxidation and a lack of growth factors. A cascade of molecular events begins with the misfolding of single proteins within a cell that then continue to aggregate to ultimately form e.g. plaques (Abeta), tangles (Tau) and Lewy bodies (a-synuclein). These misfolded proteins are then exported and spread to healthy cells nearby, causing normal proteins to misfold in a process known as seeding. This process leads to cell death in various areas of the brain and is linked to a decline in cognitive function in patients with Alzheimer’s.

Reference: Soto 2003, http://www.alz.org/brain

Reference : Soto 2003, http://www.alz.org/brain

Challenges in targeting misfolded proteins

The central challenge in targeting misfolded proteins for the development of effective therapeutics and diagnostics is a product’s ability to differentiate, or conformationally select, between a misfolded protein and a normally-folded protein. The ability to create medicines that are highly specific for only the misfolded forms of the proteins reduce the risk of side effects and are central to the development of effective therapeutics for neurodegenerative diseases.


AC Immune’s approach

We use our two unique proprietary platform technologies, SupraAntigen™and Morphomer™, to discover, design and develop disease modifying therapeutics and diagnostics to target misfolded proteins. The technology platforms are our engines for generating novel antibodies, vaccines and small molecules that are designed to bind to their targets with high affinity and conformational specificity. All of our products and our development programs have been derived from our proprietary platforms.


The diagram shows how our therapies aim to intervene in the key pathology steps involved in neurodegenerative diseases: (1) prevent misfolding; (2) promote disaggregation;
(3) inhibit spreading; and (4) prevent seeding in healthy cells.