PSY-130/131 – a reprofiled molecule for Alzheimer's disease
Drug development has for decades been driven by the idea that everhigher specificity and selectivity of new drugs would solve the pipeline problems of the pharmaceutical industry. Gene-based, high-throughput screening of vast chemical libraries and transgenic animal models for efficacy were considered the methods of choice.
Today, the emerging field of Systems biology teaches us that the genetic framework of organisms with relatively small numbers of genes is unfolding on the individual level to the enormous complexity of dynamic protein interactions. The same molecular pathways and gene products functioning in normal and healthy cellular signalling, "derail" under pathological conditions. The degree of redundancy and compensation and the flexibility of these pathways is mainly regulated and shaped by dynamic posttranslational modifications of proteins.
On this background, ProteoSys investigated the reprofiling of existing small molecule drugs for additional and novel modes of actions and thus novel disease indications. This approach has the advantage of known safety profiles for established lead compounds providing a fast and efficient avenue towards clinical phases.
The specific knowledge of dynamic changes of protein biomarker patterns in models for CNS diseases and in the proprietary in vitro neuronal stem cell cultures lead to a selection of candidate substances. Their novel modes of action and efficacies were further validated by chemical proteomics and in vivo disease experiments.
Based on its relational protein databases, substances with known structure-activity properties were selected. The proprietary stem cell assay enabled us to efficiently test the substances for their neuroprotective properties.
This was then followed by our chemical proteomics in order to understand the novel target and to provide insight in the potential second mode of action. Final preclinical validation took place in various animal models and an extensive clarification of the new mode of action was completed before the substance went directly into clinical phase II.
The substances have been outlicensed to AC Immune, Lausanne. Phase II for Alzheimer’s disease should be concluded in 2011.