Novel modulators of Abeta42 synthesis - The route towards primary prevention in AD

Purpose and goal

The objective of the project is to develop a preventive therapy for Alzheimer’s disease. The project is in late preclinical phase and we have during the last year successfully delivered on our objective, i.e. a candidate drug (CD), denoted AZD678. A variety of different studies and analysis have demonstrated that ACD678 displays the desired activity and tolerability. These encouraging data have resulted in a large external interest and to the formation of a new company, AlzeCure Pharma AB, which will further develop ACD678 towards clinical development.

Expected results and effects

ACD678 is a so-called gamma secretase modulator (GSM), which decreases Alzheimer Abeta42/40 production and increases Abeta37/38 production without affecting the total activity of the gamma secretase enzyme. We have been able to show that ACD678 indeed exhibit these important features and that it does not affect other gamma-secrease regulated processes in the body. We have also, in initial and short duration toxicology studies, demonstrated that ACD678 is tolerable at therapeutic doses in vivo, data that strongly supports further preclinical development of ACD678.

Planned approach and implementation

The project has focused on characterizing the effect of ACD678 on the process of Alzheimer Amyloid42 amyloid formation and on its tolerability as a therapeutic drug. We have performed experiments and analysis using specific cellular models and analytical methods to explore the primary pharmacology of ACD678. In addition, we have administered ACD678 at different doses to rats and studied to what extent it may potentially affect different organs and functions using a number of different analytical and histopathological methods.