2010 Award Winners
Award-winning project: Clinical diagnosis of lysosomal storage diseases in Central and Eastern Europe
Project partners: Genzyme CEE GmbH | Steinbeis-Transferzentrum Biopolymeranalytik / Proteinchemie und Proteomanalytik an der Universität Konstanz
Lysosomal storage diseases (LSDs) are a group of predominantly genetic metabolic disorders caused by a loss of activity in lysosomal enzymes. This metabolic dysfunction leads to severe symptoms which, without treatment, are often fatal even in childhood, including, amongst others, organ enlargement and heart muscle atrophy. Of the approximately 60 known LSDs to date, some can already be treated with enzyme replacement therapy, which offers a high chance of recovery once a definitive diagnosis has been made. However, reliable and rapid diagnosis remains a major challenge, meaning that those affected often die before they can receive treatment.
The Steinbeis Transfer Centre for Biopolymer Analytics / Protein Chemistry and Proteome Analysis at the University of Konstanz has developed two biochemical methods for the diagnosis of LSDs using fluorescence spectroscopy and mass spectrometry, and has validated them for clinical diagnosis in collaboration with Genzyme CEE GmbH in Konstanz and the Laboratory for Bio-Mass Spectrometry at the University of Timisoara in Romania. The quantitative determination of reaction products – and thus the activity of LSD enzymes – in blood using the ‘dried blood spot’ (DBS) method enables rapid and reliable diagnosis, particularly in Central and Eastern European countries where, until now, no effective diagnostic methods have been available.
As part of the transfer project, which was awarded the Löhn Prize, the two biochemical methods were first improved, and a diagnostic method using HPLC-tandem mass spectrometry was developed to enable simultaneous determination of multiple LSDs. In a second step, the mass spectrometric diagnostic method was established simultaneously in the laboratories in Konstanz and Timisoara and validated using clinical samples and healthy control subjects.
The methods developed can be used internationally for the highly specific diagnosis of LSDs, in broad-scale ‘screening’ investigations, and for monitoring the course of treatment. The project partners aim to use this as a basis for developing further methods to elucidate storage diseases that have hitherto been undiagnosable.