Over the last year, myaware has supported three research projects, all designed to tell us more about myasthenia gravis.

Dr Sui Wong (Moorfields Hospital London), in conjunction with Professor Paul Maddison (Nottingham), is following the disease course in patients initially diagnosed with ocular myasthenia, to see how many patients progress to generalised MG, and how many remain purely ocular.

Nearly 200 patients have now been recruited to this study; with serum samples collected for future analysis. This project will require a minimum of 2-year follow-up from the last-recruited patient and therefore the envisioned date for this modelling theory to be complete is the end of 2021. We are delighted that this study has also led to an international collaboration, which has developed a new rating scale for Ocular Myasthenia, (OMGRate). Dr Wong is pleased to announce that this work will be published soon in the scientific journal Neuro-ophthalmology.

Dr Phil Ambrose who is working with Professors Maddison and Irani (Nottingham and Oxford) has continued recruiting new patients for the late-onset myasthenia gravis (LOMG) prospective study which began with funding from myaware in 2013.

This study has already shown that the number of diagnoses per year in the South Nottinghamshire and Derbyshire areas is not increasing as previously thought. It is hoped that a new study will be carried out to monitor this trend. In total, 213 patients have been recruited into the clinical phenotyping group. Clinical and immunophenotyping (of this group of LOMG patients), seeks to understand the underlying cause of myasthenia gravis, by identifying the changes which occur in the immune system and trigger the onset of the condition.

The blood samples collected from these patients will play an important role in future research. The database has been created to house full data regarding the symptoms, treatments and details about the quality of life of the patient over a 3 year period from diagnosis. From these blood samples the team have started to study the different parts of the immune system involved in myasthenia such as the B cells. In myasthenia gravis and other similar diseases there are a small number of abnormal B cells that develop and react to one’s own body. Another part of immune system is the T Cells, which help the B cells to produce antibodies. Under certain conditions these T cells expand or proliferate and Dr Ambrose is looking at ways of regulating this expansion and altering the disease process.

Professor David Beeson and his student Mirela Panea (Oxford) are studying the congenital myasthenic syndromes. CMS is a group of inherited disorders that affect the signal transmission at the neuromuscular junction. These disorders share the clinical feature of fatigable muscle weakness. In the group of CMS patients with mutations in the molecule DOK7, neurotransmission does not function optimally due to small and destabilised neuromuscular junctions. DOK7 amplifies the signalling from muscle-specific receptors which are responsible for the formation and stabilisation of the neuromuscular junction. Recent tests have shown that large amounts of DOK7 protein in muscles generate enlarged neuromuscular junctions, which are very efficient in signal transmission and have no reported detrimental effects.  Therefore, this study aims to identify small molecules that can specifically increase the amount of DOK7 in the affected muscles and use this as a potential therapy for CMS.

Professor Beeson’s group has now studied a collection of 5431 small muscle-specific compounds, to see if any act on muscles to raise the levels of DOK7.  Initial screening produced 37 potential molecules that produced significant increase and have been further tested in our biological activity assay, which aims to test compounds’ ability to form a synaptic structure in vitro. Two compounds showed potential in doing this and so these compounds have now being further investigated. They will provide the basis for a more detailed analysis of the effects of DOK7 increase in cell culture biological assays and ultimately for in vivo testing.

Finally, in future work we are delighted that a recent substantial legacy gift restricted for the use of research only, will fund a brand new 3 year fellowship. This funding has been award to Dr Maria Leite and will start in 2020, with the aim of developing a UK-wide database of patients with MG. This database will allow clinicians and medical researchers to investigate the clinical history of the disorder, obtain information on the gender, age of onset, clinical symptoms and response to treatment in a statistically meaningful number of patients. Such a large database can also serve as a valuable resource of knowledge for studies of disease pathogenesis, variability and treatment outcomes.

At the end of a decade in which myaware-funded projects have been at the forefront of research into myasthenia, all of the research teams have expressed how very grateful they are to all the patients who have joined the projects, come to the clinics and given permission for the teams to use their blood and data. Without the help from the patients none of these projects would progress.

Myaware receives no government or NHS funding and therefore is fully reliant upon the kindness and generosity of people like you to ensure funding for our research projects.

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