Another project led by Dr Beeson, termed ‘Super Synapses’, focused on DOK7-driven CMS. Dr Beeson’s work has enabled categorisation of different types of CMS, DOK7 being one of them. With this organisation, stratification of treatment for patients became more possible. Before the discovery of DOK7-driven CMS, treatments were restricted to medications such as pyridostigmine, fluoxetine, or quinidine, which target pathways associated with acetylcholine. With further insight into the DOK7 mutation, patients were offered better options with improved outcomes in ephedrine or salbutamol, which are agonists of the β2-adrenergic receptor. If a medication is referred to as an ‘agonist’, it means it binds to a receptor in the cell or on the surface. It will generally enable the same action as a substance that normally binds to the receptor.

With a growing interest in the biology of the DOK7 protein, the Beeson group looked to emulate previous work completed by Dame Kay Davies, where it was seen that increasing production of the protein Utrophin had a positive effect on Duchenne Muscular Dystrophy. It was theorised that similar improved expression (also referred to as ‘upregulation’) of DOK7 may have potential as a therapeutic approach. They observed that this increased expression of DOK7 led to enlarged synapses – termed ‘super synapses’ as per the project title. A synapse is the term used to describe the space between two cells. It is the site of communication between cells, and an important example of a synapse in terms of myasthenia is the neuromuscular junction. At the neuromuscular junction, messages between nerves and muscles are shared. In myasthenia, the transfer of information between nerves and muscles is impaired. The increased size of the synapse through upregulation of DOK7 appeared to have no detrimental effect but rather increased the efficiency of these messages being passed between cells.

With this in mind, it became the goal of the Super Synapse project to identify potential medications that were able to up-regulate DOK7 protein. It was hoped that a drug capable of this would be able to treat most types of CMS and potentially be hopeful in autoimmune-focused myasthenias. As of 2019, five potential medicines had been identified through a reported system developed by the Beeson group. There is a view to move these medications into testing with an animal model for further verification.

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