Projects

The aim of the BioDEL project is to develop human in-vitro test systems for standardized and predictive high-throughput testing of PROTACs and other molecular degraders, and to establish carrier platform technologies that will allow the rational development of a customized carrier system for the targeted delivery of a specific PROTAC molecule. In addition, predictive in-vitro to in-vivo correlations (IV-IC) and in-silico models will be developed to enable future successful therapeutic use of PROTACs.

Mitochondrial DNA (mtDNA)-associated Leigh syndrome (MILS) is an untreatable rare brain disease in infants and children. MILS is typically caused by mtDNA mutations in the ATP-generating subunit MT-ATP6. This consortium has employed neural cells generated from MILS patients via cellular reprogramming to carry out large-scale screenings using repurposable drugs, thereby allowing the identification of new therapeutic strategies. We identified phosphodiesterase 5 inhibitors (PDE5i) as a potential therapeutic option for MILS and confirmed its positive effect in extensive multi-omic studies. Compassionate use of PDE5i was shown to be beneficial in MILS patients. An multi-national clinical trial and a concrete path towards a new standard of care for MILS has been initiated.

The project aims at systematically collecting evidence for the co-morbidity between COVID-19 and neurodegenerative diseases (such as Alzheimer’s and Parkinsonism). One key goal of COMMUTE is to unravel the mechanisms underlying the possible link between SARS-CoV-2 and neurodegeneration and to generate models that allow for personalized risk assessment for COVID-19-induced cognitive decline. The other major goal of COMMUTE is to develop cellular assay systems that identify drug-repurposing candidates that prevent or reduce COVID-19-induced risk for neurodegeneration. Finally, the ethical and legal work in the consortium will come up with recommendations for handling ethical and legal aspects of virus-induced neurodegenerative disease risk.