Missing Protein Restored in Patients with Muscular Dystrophy

21.08.2014 - (idw) Universitt Basel

Advances in the treatment of muscular dystrophy: For the first time, a research team has succeeded in restoring a missing repair protein in skeletal muscle of patients with muscular dystrophy. Researchers from the University and the University Hospital of Basel, Department of Biomedicine and Clinic of Neurology, report their recent findings in the scientific journal Science Translational Medicine. When muscle cell membranes are damaged, the repair protein dysferlin is activated and reseals muscle membrane tears. If this repair protein is altered due to a genetic mutation, the body's own quality control system (the so called proteasome) identifies the protein as being defective and eliminates it. Without dysferlin, injured muscle cell membranes cannot be repaired, which leads to progressive loss of skeletal muscle cells and thus to muscle wasting. It appears that the body's own quality control system neutralizes mutated dysferlin even if the mutation does not actually impair its repair function.

Repair protein reactivated

The research group led by Professor Michael Sinnreich at the Departments of Neurology and Biomedicine at the University and the University Hospital of Basel had previously demonstrated that proteasome inhibitors can reactivate mutated dysferlin proteins in cultured muscle cells from muscular dystrophy patients. The inhibition of the exaggerated cellular quality control enables the altered repair protein to regain its function and to repair damaged muscle membranes.

Long-term trial planned

For Head of Research Michael Sinnreich, the new findings serve as groundwork for future long-term clinical trials: These findings could be of importance for the treatment of patients with muscular dystrophy as well as other, previously incurable genetic diseases.

The study was funded by the Gebert Rf Foundation, the Uniscientia Foundation, the Swiss National Science Foundation, the Neuromuscular Research Association Basel, the Association Franaise contre les Myopathies, the Swiss Muscle Society as well as the Swiss Foundation for Research on Muscle Diseases, and conducted with the support of the Clinical Trial Unit of the Basel University Hospital.

Original source B. A. Azakir, B. Erne, S. Di Fulvio, G. Stirnimann, M. Sinnreich Proteasome inhibitors increase missense mutated dysferlin in patients with muscular dystrophy Science Translational Medicine (2014) | doi:

More information Professor Michael Sinnreich, Director of the Neuromuscular Center, Clinic of Neurology, University Hospital of Basel & University of Basel, Department of Biomedicine, and phone: +41 61 265 25 25 (University Hospital of Basel switchboard), email: michael.sinnreich@unibas.ch

Link:
Missing Protein Restored in Patients with Muscular Dystrophy