Inherited Myopathies

The most common form of congenital myopathy is nemaline myopathy. Nemaline myopathy was first described by a pathologist, Dr Douglas Reye at Royal Alexandra Hospital for Children (now known as The Children’s Hospital at Westmead) in 1958. However, this honour was recognised only very recently. Children with nemaline myopathy are usually weak from birth and have problems with their feeding and breathing muscles. Some children do not present with muscle weakness until childhood whilst other patients present in adulthood. Characteristically, patients with nemaline myopathy have accumulations in their muscle cells called “nemaline bodies” (rods). We do not know how these accumulations occur. In recent years, genetic defects in 5 different genes, including actin and tropomyosin, have been identified to cause nemaline myopathy. Actin and tropomyosin are highly abundant in muscle and play major roles in muscle contraction. The Congenital Myopathy team study the causes and consequences of nemaline myopathy and have produced landmark reports influencing our understanding of this disorder.

The team are now developing laboratory models to mimic this disorder in vitro. Our goal is to understand how the disruption of the internal muscle structure affects overall muscle function and determine therapies to alleviate this disorder. We have already developed a tissue culture of nemaline myopathy by growing muscle cells in the laboratory that express mutations in actin and tropomyosin (based on those identified in patients). These muscle cells produce nemaline-like bodies similar to those observed in patient muscle cells, hence making this an excellent model to study this disease. Using this model we will study how rod formation occurs and will test future therapies for nemaline myopathy.

We are also currently developing a mouse model of nemaline myopathy which will provide us with an opportunity to study the causes of muscle weakness in a whole animal model. Our team are working on this aspect of nemaline myopathy and more detailed information is provided in their project descriptions. This mouse model will be used to study rod formation and to test future therapies for nemaline myopathy.