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Jul 23, 2019

Multifunctional Anti-Amyloid Peptides

Life Sciences, Neurology/CNS

  • Macrocyclic peptides with drug-like properties
  • Highly potent inhibitors of Aβ amyloid self-assembly
  • Promising in vivo data from Alzheimer’s mouse model

Your contact

Dr. M. Charlotte Hemmer

E-Mail:
chemmer@baypat.de
Phone:
+49 (0) 89 5480177 - 29
Reference Number:
B78094 / B82009 / B84076

Challenge

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.

Innovation

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as a potent inhibitor of amyloidogenesis in several in vitro assays and a mouse model of Alzheimer’s disease (unpublished data).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

Commercial Opportunities

  • 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

Development Status

TRL Level 3.5

References

  • 1

    doi: 10.1002/anie.201802979

Interested? Get in touch!

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