Genes, mechanisms and models of congenital myasthenic syndromes Professor David Beeson, Oxford University The myasthenia can be divided into those that arise as a result of antibodies attacking the patient's own body (myasthenia gravis and LEMS) and those that are present from birth due to inheritance of defective genes (congenital myasthenic sydromes) . My group works on these inherited myasthenias. We aim to identify the underlying genetic defect in these patients and determine how the altered gene actually causes muscle weakness. This knowledge will allow us to advise the clinicians on the most appropriate treatment for each patient. We have recently, identified mutations in two new genes that can cause CMS, and are currently determining precisely how these changes result in muscle weakness seen in the patient. Another arm of our research involves treatments that have been re-introduced over the last few years, and that have proved remarkably effective in treating sub-groups of the congenital myasthenic syndromes. These are the β2-adrenergic receptor agonists ephedrine and salbutamol. We have been studying these drugs in the laboratory to see if we can understand how they produce their effect. In patients with CMS, the genetic defect often causes the chemical signal between the nerve and the muscle to become unstable, and so the patients muscle strength is affected. We have been able to show that these drugs do in fact have a direct effect on this junction (the neuromuscular junction) making it more stable. This results in improvement in the signal transmission from the nerve to the muscle. The next step is to see if we can find related drugs that may be more effective. More information on Professor Beeson’s research is available here.