Researchers Discover Gene Targets In Emery-Dreifuss Muscular Dystrophy

By C. Rajan, contributing writer

An international team of researchers has just discovered new genetic targets responsible for an incurable muscle-wasting disease, Emery-Dreifuss muscular dystrophy (EDMD).

Led by investigators at the University of Leicester, the researchers found two new target genes, SUN1 and SUN2, for EDMD, which opens the possibility of developing potential drugs to treat this debilitating disease. The University of Leicester team collaborated with research groups in University of Greifswald in Germany, the Institute of Molecular Genetics in Italy, and Columbia University, USA.

EDMD is a rare inherited, progressive, muscle weakening condition which ultimately leads to muscle wasting, joint stiffening, and heart problems. So far, only six genes responsible for EDMD have been identified. Despite rigorous screening, at least 50 percent of patients with EDMD do not show any detectable mutations in the six identified genes. This research study has now discovered two more genes linked to the disease.

According to the researchers, EDMD is caused by mutations in one of several genes that are responsible for producing proteins that form a structural scaffold for each cell's nucleus containing the DNA.

Sue Shackleton, lead researcher at Leicester and senior lecturer in Biochemistry, said, "Our research has identified two new genes, SUN1 and SUN2, that are responsible for causing EDMD in some of these individuals. The proteins produced by these genes also form part of the structural scaffold of the nucleus. Importantly, we have identified a novel way in which these mutations act in muscle cells. Further research is now needed to investigate this new potential disease mechanism and to increase our understanding of how nuclei are positioned in normal muscle cells, but our findings offer the possibility for a novel drug target for the treatment of this disease in the future."

Shackleton also says that EDMD affects around 1,000 people in the U.K. The symptoms of muscle wasting and joint stiffening begin in early childhood and worsen over time. By adulthood, most individuals also develop heart problems, increasing their risk of heart attacks. At the moment there is no cure for this disease and no effective treatment for the symptoms.

Marita Pohlschmidt, Director of Research at the Muscular Dystrophy Campaign, said, "We welcome the encouraging results of this study, which has identified two new genes which can cause Emery-Dreifuss muscular dystrophy. In the future, this will give more people an accurate genetic diagnosis, helping them to understand the risk of passing it on to their children and to make informed choices with regards to planning for a family. An accurate genetic diagnosis also means that patients will receive more precise information about the prognosis of the condition. Most importantly, a better understanding of the condition is crucial for the development of treatments for this complex and devastating condition."

The work was published last week in the journal PLOS Genetics.