Congenital myasthenic syndromes (CMS) is the term used to describe inherited disorders of neuromuscular transmission. Mutations in genes related to neuromuscular function can cause muscle weakness and other symptoms of CMS to display in primarily early childhood. Due to the nature of CMS, the immune system is not involved as it traditionally is with other myasthenias. This has meant a significant level of work has been carried out to identify the causal genes and improve diagnosis. To date, there have been fourteen mutations identified to be causal for these disorders. The subtypes of CMS are linked to the expressed protein in which mutation occurs. This can include DOK7, Musk, b2-Laminin, AChR, GFPT1, or Plectin.

Myaware has funded several projects aiming to broaden our understanding of CMS and a great number of these projects have been spearheaded by Dr David Beeson and his group, currently based at the University of Oxford. Dr Beeson’s research has enabled categorisation of the different CMS’, dividing them by subtype, gene involved, and the main pathology for each syndrome. The distinguishing features of these syndromes has also been identified, such as the typical age of onset and presenting symptoms.

One project of note undertaken by Dr Beeson and funded by myaware was one that explored the genes, mechanisms, models, and treatment for hereditary myasthenia. Specifically, this project looked at proteins that functioned at the neuromuscular junction and the genes responsible for their expression. This project identified three genes; ALG2, ALG14, and DPAGT1, in which mutation can cause CMS. Using the knowledge of these three genes then meant this project could further investigate how their function affects myasthenia. By understanding these mechanisms, appropriate patient treatment can become much more achievable as they present new targets for drugs and other therapeutics. Finally, this project also underlined the importance of maintaining proper regulation of a process called glycosylation. When proteins are expressed in the body, they can undergo modifications that enable different functions. Glycosylation adds a carbohydrate to a target, in this case a protein. Without this process, the genes identified by this project are unable to carry out their correct functions, which can lead to the development of myasthenic symptoms.

To read more about Dr Beeson’s continued work in myasthenia research, click here to visit his page on the University of Oxford website.

Past Research Projects