MSD Action Foundation announces research partnership with University of Southampton, UK in collaboration with University of Bielefeld, Germany and University Medical Center Gottingen, Germany – 14th August 2018
Research project: Identification and Development of FGE Stabilizing Molecules: Towards a Therapy for Multiple Sulfatase Deficiency.
Professor Thomas Dierks (top left), Professor of Biochemistry, University of Bielefeld, Germany.
Dr Karthikeyan Radhakrishnan (top right), Post-doctoral fellow, University of Bielefeld, Germany.
Dr Lars Schlotawa (bottom left), Consultant for Paediatrics, University Medical Center Gottingen, Germany.
Dr Matthias Baud (bottom right), Lecturer in Medicinal Chemistry and Chemical Biology, University of Southampton, United Kingdom.
Research Summary: Multiple Sulfatase Deficiency (MSD) is an extremely rare, fatal, yet untreatable condition with an urgent need for therapy development. The loss of function of an enzyme called Formylglycine generating enzyme (FGE, encoded by the SUMF1 gene), was discovered as the molecular basis for MSD. Based on several studies on FGE, we know that alterations in FGE structure as a result of SUMF1 mutations reduce its stability and result in its loss of function. We are investigating whether stabilization of the structure of FGE in MSD patients could rescue its function and thereby cure or at least mitigate the severity of the disease. As a new therapeutic strategy to treat MSD, we are currently exploring whether small molecule drug candidates can be devised that stabilize and thus reactivate FGE function in cells. These molecules are supposed to bind to the surface of unstable FGE protein and stabilize its conformation, resulting in an increased activity. Our efforts are focused on the development of such “molecular plasters”, using complementary techniques across biochemistry, biology and chemistry in our laboratories in Bielefeld, Göttingen and Southampton. Through this collaborative project, we hope to discover new lead molecules that will form the basis of future generations of much needed drugs to treat MSD.