Advancing a peptide therapeutic for Alzheimer's through clinical trials with Dr Dieter Willbold

We spoke to Dr Dieter Willbold, Director, ICS-6 Structural Biochemistry at Forschungszentrum Jülich, about his work on a peptide therapeutic in development to treat Alzheimer's.

What current challenges are you facing for advancing your promising peptide for Alzheimer's disease through clinical trials?

'Our main focus at the moment is to finish all the necessary preclinical tox and safety tests in order to soon get permission for a clinical phase I study with our drug candidate.

One challenge for developing therapeutics like ours that target specific aggregate species, lies in the lack of suitable analytics to measure target engagement, because most methods don't differentiate between different aggregate sizes. In addition to cognitive behavioral tests, we ourselves have therefore developed novel methods to measure efficacy and target engagement .e.g. QIAD (short for quantitative determination of interference with aggregate size distribution; Brener et al., Scientific Reports 2015), which measures Abeta oligomer elimination efficiency.'

What are the advantages of peptide therapeutics over small molecules, antibodies and other protein therapeutics?

'Small molecules often lack specificity, and this can lead to serious side effects and autoimmune responses. On the other hand protein-based therapeutics like antibodies possess high target selectivity and are made of natural components, but they are very big and expensive molecules. They often suffer from low oral bioavailability.

Small peptides can offer the best of both worlds in some respects: They are more target specific than small molecules but easier to produce than protein based drugs. Our drug candidate is made solely from D-enantiomeric amino acid residues and has surprisingly good oral bioavailability.'

Where do you see innovation happening in the peptide field over the next 5 years?

'Innovation will certainly happen in the production of peptides (cost reduction) and in the formulation of peptides (increase oral bioavailability).'