Advanced, automated compound screening for the identification of therapeutic agents in Multiple Sulfatase Deficiency.
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. Decreased activity of sulfatases can be measured in cell lines derived from MSD patients that are cultivated in a laboratory. They can also be treated with specific drugs. Successful treatment increases sulfatase activities in the cells and this is a first step towards the development of a cure for MSD.
We developed a method that allows testing of a large number of drugs by treating the MSD cells in parallel in a short time. Only recently, we were successful in identifying one drug out of 800 tested that can effectively increase sulfatase activities. This drug has a high potential to become a future cure for MSD after efficacy is established in further experiments. In our project proposed here, we aim for making our already validated screening method automated to test even more drugs and drug-like substances in parallel with higher accuracy/precision. We will aim for screening up to 5600 drugs and drug-like agents for their ability to re-establish sulfatase activities in MSD cells. So-called hits derived from this experiment will be analysed in follow-up experiments and could become alternative or additional potential treatment options for MSD.
- Award Date
- 01 July 2022
- Award Value
- Principal Investigator
- Dr Lars Schlotawa
- Host Institution
- Fraunhofer ITMP
- HRCI-HRB Joint Funding Scheme