Gene- and protein-signatures as GPS for patients with neuromuscular diseases

Neuromuscular diseases (NME), which can be both genetic and acquired, are characterized by a usually progressive weakness of the skeletal muscles (and often also of the heart muscles) and can be fatal. Despite enormous technological progress in gene analysis, about 50% of presumed genetically determined cases remain unsolved, which not only significantly delays or even prevents a possible therapeutic intervention, but also leads to a “diagnostic odyssey” of patients, which in turn causes high costs for the health system. The necessary improvement of the still very limited treatment concepts for neuromuscular diseases requires a more precise understanding of the molecular causes of these diseases. The clarification of the exact pathophysiological cascades can allow the definition of uniform therapeutic intervention procedures for (rare) neuromuscular diseases and thus help to increase the interest of the pharmaceutical industry in the development of appropriate drugs and thereby counteract the “rare disease problem”.

Using state-of-the-art omics technologies and microscopic methods, NME-GPS will systematically and radically solve this problem by setting up a targeted proteomic-based assay for the robust quantification of causative proteins and comparing its measurement results with the results of DNS analyses and CARS and Raman microscopic examinations. Using a specially generated algorithm, it will be possible to determine “patterns” of gene & protein co-regulation (proteogenomics) that accurately predict the causal genetic defect and enable a new classification of hereditary and acquired neuromuscular diseases based on their histological-biochemical properties. In the future, this will allow antibody-independent analysis of all NMW-relevant proteins, thus enabling the most comprehensive protein diagnostics of neuromuscular diseases to date. Morphological results in correlation with the results of further proteomic analyses such as global profiling, the quantification of phosphoproteins and degradation products will lead to a new classification scheme of this disease group and at the same time allow the definition of uniform and specific pathomechanisms, an aspect that is essential for the testing of new therapeutic intervention concepts.

This reliable diagnosis will have a considerable influence on improved genetic counselling and timely therapeutic intervention. In this sense, NMW-GPS will revolutionize the diagnostic procedure for neuromuscular patients and, by defining new therapeutic intervention concepts, counteract morbidity, mortality and the resulting costs for the healthcare system.

The work at ISAS aims to generate proteomic and morphological data using muscle biopsies obtained from patients with neuromuscular diseases, which will serve as a basis for the implementation of new algorithms for the future improved diagnosis and treatment of patients with this disease group.  At ISAS the research groups Protein Dynamics, Standardization, CARS-Microscopy and Lipidomics of the Department of Bioanalytics work closely together.

In addition to ISAS, cooperation partners in the NMW-GPS project are the Department of Pediatrics ( (Neuropediatrics) of Essen University Hospital, the MVZ institute for Clinical Genetics and Tumor Genetics in Bonn and INOFRM GmbH in Aachen.