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.
Now the team has translated these findings into clinical application and has, in a proof-of-principle study, restored the missing dysferlin protein in skeletal muscle of patients with muscular dystrophy. Three patients carrying a dysferlin mutation received a single systemic dose of a proteasome inhibitor. After only a few days the patients’ musculature produced the missing dysferlin protein at levels that could be therapeutically effective.
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 Rüf Foundation, the Uniscientia Foundation, the Swiss National Science Foundation, the Neuromuscular Research Association Basel, the Association Française 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.
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:
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: email@example.com
Olivia Poisson | Universität Basel
Epigenetic Modification Increases Susceptibility to Obesity and Predicts Fatty Liver Later in Life
23.05.2016 | Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke
Lab cell study shows that HOXA5 protein acts as tumor suppressor in breast cancer
20.05.2016 | Johns Hopkins Medicine
Characterization of high-quality material reveals important details relevant to next generation nanoelectronic devices
Quantum mechanics is the field of physics governing the behavior of things on atomic scales, where things work very differently from our everyday world.
When current comes in discrete packages: Viennese scientists unravel the quantum properties of the carbon material graphene
In 2010 the Nobel Prize in physics was awarded for the discovery of the exceptional material graphene, which consists of a single layer of carbon atoms...
The trend-forward world of display technology relies on innovative materials and novel approaches to steadily advance the visual experience, for example through higher pixel densities, better contrast, larger formats or user-friendler design. Fraunhofer ISC’s newly developed materials for optics and electronics now broaden the application potential of next generation displays. Learn about lower cost-effective wet-chemical printing procedures and the new materials at the Fraunhofer ISC booth # 1021 in North Hall D during the SID International Symposium on Information Display held from 22 to 27 May 2016 at San Francisco’s Moscone Center.
Staphylococcus aureus usually is a formidable bacterial pathogen. Sometimes, however, weakened forms are found in the blood of patients. Researchers of the University of Würzburg have now identified one mutation responsible for that phenomenon.
Staphylococcus aureus is a bacterium that is frequently found on the human skin and in the nose where it usually behaves inconspicuously. However, once inside...
Using ultrashort laser pulses an international team at the Max Planck Institute of Quantum Optics and the Ludwig-Maximilians-Universität Munich has managed to manipulate the positions of atoms in hydrocarbon molecules.
Light can conduct the play of atoms and molecules in the microcosm. Humans manage to interfere with this play. Researchers from the Laboratory of Attosecond...
20.05.2016 | Event News
19.05.2016 | Event News
17.05.2016 | Event News
23.05.2016 | Information Technology
23.05.2016 | Architecture and Construction
23.05.2016 | Earth Sciences