The CHAMPION research project addresses the development of novel therapeutic options for Multiple Sulfatase Deficiency (MSD), a genetic lysosomal disorder characterized by impaired activity of multiple sulfatases. MSD is a rare, severe, and currently incurable childhood neurodegenerative disease. The project builds upon promising preliminary results from high-throughput screening of bioactive compounds and will systematically evaluate selected candidates with the aim of identifying compounds suitable for further preclinical development. The research outcomes will contribute to a better understanding of the therapeutic potential of these novel compounds and provide a scientific foundation for their future translation into clinical testing. The CHAMPION project is important not only for the treatment of MSD but may also contribute to the development of new therapeutic approaches for related lysosomal disorders, for which current treatment options remain insufficient.

Multiple Sulfatase Deficiency (MSD) is an extremely rare, fatal, yet untreatable condition. It is caused by the inherited deficiency of an enzyme (called FGE) that activates a whole family of 17 other cellular enzymes named sulfatases. Sulfatases are indispensable for the degradation of a subset of intracellular molecules. Thus, patients with MSD and deficient sulfatases show intracellular storage of such molecules that are not degraded properly. The storage affects all organs and results in clinical symptoms like developmental delay, bone disease, and loss of motor and cognitive skills. A putative therapy for MSD could be using drugs and drug like substances that have been developed for other diseases if they show effects on MSD in laboratory testing. We identified 56 substances that might be able to become a therapy for MSD. In the project we propose to investigate these substances in MSD disease models including MSD mice and asses their potential to become a cure for MSD: We will create and compare the best form for application of the substance to patients, e.g. as tablets, capsules or fluids considering the specific needs of MSD patients. We will also try to find out how effective drugs cure MSD in cells of and identify alternative drugs that could work in the same way. In addition, we will try to find out whether the compounds that may cure MSD could also be a therapy for diseases that are similar to MSD. From the start of the project we will get help from experts in drug development, clinical experts for MSD and most important a father with a son with MSD. They will all take care that the project will reveal a successful outcome with results useful for MSD patients.