Anti-myeloid peptides to combat Alzheimer's

Alzheimer‘s disease (AD) is a yet incurable neurodegenerative disease that slowly and progressively worsens. The most common early symptom is difficulty in remembering recent events and as the disease advances, symptoms include problems with language, disorientation, mood swings, loss of motivation, self-neglect and behavioral changes. Ultimately, bodily functions are lost leading to death. AD is characterized by extracellular deposition of amyloid-ß (Aß). Despite the established link to amyloid plaques of ß-amyloid peptide (Aß) in the brain, all anti-Aß therapeutic strategies have so far failed e.g. antibody-based approaches aimed at blocking amyloid self-assembly. However, the development of anti-amyloid compounds is an important target of AD-related research. For this reason, there is an urgent need to develop novel classes of amyloid inhibitors.

MCIP 2E was confirmed as a potent inhibitor of amyloidogenesis in several in vitro assays and a mouse model of Alzheimer’s disease (unpublished data). Its drug-like properties include small size (<20 amino acids), high solubility, potent amyloid inhibitor function (nanomolar IC50) and Aß-40(42) binding affinity, target selectivity and blood brain barrier (BBB) permeability (determined using in vitro models). In light of the extremely low BBB as one of the weak points of antibody-based approaches, the above listed properties make MCIPs suitable drug candidates.

• Effective production by routine solid phase peptide synthesis
• Good proteolytic stability in human plasma (in vitro)
• Effective crossing of human blood brain barrier (in a cell model)
• Promising data from behavioral tests with no observed in vivo toxicity in mouse model

TRL Level 4