Projects

Cooperation partners: Abberior GmbH, Lead Discovery Center GmbH, Max Planck Institute for Medical Research.

Previous screening methods for the characterisation of new pharmacological agents are capable of testing thousands of substances for their efficacy in a relatively short time. However, they often only show whether an active substance interacts with a cell or not. The actual mechanism of action remains hidden and is only revealed by looking through a microscope. However, the microscopy methods available so far are very slow or do not achieve the resolution required to resolve the smallest beta particles, for example receptors in the plasma membrane of the cell.

The High Resolution Drug Screening (HRDS) project, funded by the Federal Ministry of Education and Research (BMBF), has set itself the task of developing a new method based on ultra-high resolution microscopy for the characterisation of active substances for drugs. To achieve this, the research team led by Göttingen scientist and Nobel laureate Professor Stefan Hell (Director at the Max Planck Institute (MPI) for Multidisciplinary Natural Sciences in Göttingen and at the Max Planck Institute for Medical Research in Heidelberg) together with Dr. Gerald Donnert (Abberior GmbH, Göttingen) and Dr Bert Klebl (Lead Discovery Center GmbH, Dortmund) as well as Professor Stefan Jakobs (Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Göttingen) a combination of automated ultrahigh-resolution STED microscopy with subsequent machine learning-supported data evaluation. 

The project will be funded with 11.7 million euros over the next three years as part of the BMBF funding guideline "KMU-innovativ: Photonik und Quantentechnologien".

As part of a drug repurposing project for the development of a therapy for a rare neurometabolic disease, the working group has succeeded in identifying a group of therapeutically effective substances that are about to be used in a very first clinical trial for the disease. The disease in question is multiple sulphatase deficiency (MSD), a neurodegenerative, multisystemic, severe disease from the group of lysosomal diseases with no treatment options. The disease is characterised by a simultaneous loss of activity of all cellular sulfatases and the resulting pathophysiology. Following the development of a high-throughput screening assay, two retinoids were identified that, alone and in combination, increased sulfatase activities in MSD cells and normalised the in vitro pathophysiology. As these are drugs authorised for another treatment indication with a known spectrum of side effects and toxicology, they are suitable for use in another indication, in this case MSD (drug repurposing). As part of the EU-funded joint project REMEDI4ALL, one of the retinoids will be investigated in a phase I/II study in MSD patients in Göttingen in the near future. In addition to the preclinical expertise, this project benefits from the extensive clinical experience in the field of lysosomal and neurodegenerative diseases of childhood as an example of a comprehensive translational approach to the development of therapies for corresponding diseases.