Experimental Medical Science

Faculty of Medicine | Lund University


Welcome to the Muscle Biology Group

Madeleine Durbeej Hjalt, Foto K Ruona


Madeleine Durbeej-Hjalt,
PhD, Professor, Group Leader

Phone: +46 46 222 08 12

The ultimate goal of the research performed in my laboratory is to understand the pathogenesis of laminin a2 chain deficient muscular dystrophy (also known as MDC1A) and to develop a pharmacological treatment for this deteriorating disorder.

Muscular dystrophy is a general term that describes a group of inherited diseases that cause muscle weakness and muscle loss. A severe type is MDC1A, which is characterized by neonatal onset of muscle weakness, hypotonia, progressive joint contractures, inability to stand and walk, peripheral neuropathy and white matter changes. Common serious complications of MDC1A include respiratory failure and respiratory tract infection is the most common cause of death, which occurs in the first decade of life in 30% of the patients. However, most patients die in their teens. Currently, there is no cure for this devastating disease.

MDC1A is caused by mutations in the LAMA2 gene, encoding the a2 subunit of the protein laminin-211. Laminins are molecules composed of three chains (a, b and g) and are major constituents of basement membranes, the thin sheets of extracellular matrix connected to muscle, Schwann, fat, epithelial and endothelial cells. Laminin a2 chain is mainly expressed in neuromuscular basement membranes and therefore mutations in this chain affect primarily muscle and nerve cells.  

Several strategies to combat disease in mice have been explored during the last decade. Since the extracellular matrix is affected in MDC1A, many approaches were aimed at targeting the expression of extracellular matrix proteins. We have suggested that paralogous gene therapy with laminin a1 chain (mainly expressed in epithelial basement membranes) constitutes a promising therapeutic strategy for MDC1A. Yet, it is important to remember that gene therapy presents significant challenges before it becomes a practical approach to treating disease. Thus, potential novel therapeutic approaches for MDC1A treatment should also be explored. We have in two separate studies recently demonstrated that increased proteasome and autophagy activity, respectively, is pathogenic in MDC1A and that proteasome and autophagy inhibition is of great benefit in a mouse model for MDC1A. 

We hope that our studies will promote better understanding of the disease process and that they may lead to a drug therapy in patients suffering from MDC1A.

The Muscle Biology Group March 2013

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