Looking inside cells to find novel ways to treat muscle disease

Posted by ap507 at Jun 14, 2016 12:20 PM |
PhD student Caroline Shak discusses Emery Dreifuss Muscular Dystrophy and how studies can help to find a cure of the disease
Looking inside cells to find novel ways to treat muscle disease

Skeletal muscle fibre

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Muscular dystrophies are inherited diseases that lead to wasting and progressive weakening of muscles. One type, called ‘Emery Dreifuss Muscular Dystrophy’ (EDMD), displays symptoms from childhood and heavily decreases the quality of life for patients. They may become wheelchair users later in life and have an increased risk of sudden death from heart problems.

There is currently no treatment or cure for EDMD and life-long supportive care is required to maximise muscle activity and life expectancy. However understanding of an abnormal feature commonly observed in muscle disorders may give the information needed to develop a treatment for these diseases.

Abnormal cells in muscular dystrophies

Skeletal muscle cells (SMC) form the muscles that attach to our skeleton and give us strength and movement. These cells are special for two reasons. Firstly the length of most cells is a fraction of a millimetre, whereas a SMC can be up to 30 centimetres in length. Secondly, most cells have a single nucleus at its centre - a nucleus can be thought as the factory that produces nutrition for a cell. However, SMCs contain multiple nuclei (plural of nucleus), which are spaced out along its length. SMCs probably require multiple nuclei along its length so “nutrients” can be distributed throughout the cell.

Instead, research has shown that in patients with muscular dystrophies, nuclei cluster to the centre of SMCs. This phenomenon, called “nuclear clustering” is a major feature of EDMD. It is not clear how nuclear clustering occurs, and understanding of this is what may help researchers create the much-needed treatment for these muscle diseases.

Understanding how these cells result in weak muscles

As part of the on-going research in this field, I will be studying the LINC complex in the lab of Dr Sue Shackleton. The LINC complex is a group of proteins that sit on the surface of each nucleus. Through other cellular structures, they anchor to rope-like proteins called microtubules, which allow the nucleus to be pulled to different positions in the cell.

By studying the genetics of patients, the Shackleton laboratory has already identified gene mutations that cause EDMD. The mutations are thought to disrupt the connection between the LINC complex and the cellular ropes so the nucleus can no longer be pulled to the correct position. Here, “nutrients” are not distributed throughout the cell and as a result, muscles formed by the SMCs are weak.

This is exciting and important research. By further defining the roles of the LINC complex in the correct positioning of a nucleus, and how exactly this is disrupted by disease-causing mutations, researchers may be able to stop nuclear clustering. This means a treatment for muscular dystrophies could one day be available for patients.

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