Multifunctional Anti-Amyloid Peptides

Aberrant amyloid self-assembly and cytotoxicity of Aß and a-Synuclein are linked to the pathogenesis of more than 50 cell-and neurodegenerative diseases including Alzheimer's (AD), Parkinson’s disease (PD) and type 2 diabetes (T2D), the latter being epidemiologically linked to both AD and PD. For this reason, there is an urgent need to develop molecules that suppress both amyloid self-assembly and cross-seeding interactions of above peptides can be promising leads for therapeutics in AD, PD and T2D. AD-and PD-related neurodegeneration in the brain are linked to the self-assembly of Aß and a-Synuclein while T2D-related pancreatic beta-cell degeneration is linked with amyloid self-assembly of IAPP. Cross-seeding interactions between different amyloid polypeptides/proteins have emerged as possible molecular links between various different cell-/neurodegenerative diseases. Molecules that suppress both amyloid self-assembly and cross-seeding are urgently needed, however.

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confirmed as a potent inhibitor of amyloidogenesis in several in vitro assays and a mouse model of Alzheimer’s disease (unpublished data).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 3.5