Centre for Healthy Brain Ageing (CHeBA) Visiting Lecture
Oligomeric amyloid β (Aβ) is suspected of being the most toxic species in Aβ aggregation and of being responsible for development and progression of Alzheimer’s disease (AD). Development of compounds that are able to eliminate already formed, toxic Aβ oligomers is very desirable. In the recent years, we have developed all-D-enantiomeric peptides that are able to directly and specifically eliminate toxic Aβ oligomers in vitro. The in vivo proof of concept for “D3”, the lead compound of this development, was accomplished in several treatment studies. Here, we describe in vivo efficacy of the improved D3 derivative “rational design 2” (RD2). RD2 was able to reverse the cognitive deficit and to significantly reduce Aβ pathology even after oral administration in old-aged transgenic AD mice with full blown pathology and deficits. Preclinical and safety and toxicology yielded very favourable properties. Therefore, we are just about to start a first-in-human phase I clinical trial to show safety also in humans.