Myaware is currently funding five major projects. Professor Paul Maddison and his student Dr Girija Sadalage, based at Queens Medical Centre, Nottingham, have been investigating why the incidence of myasthenia gravis (MG) in the older population has been steadily increasing over the last 30-35 years. It is curious observation that the increase is much steeper in the late onset group - those aged 50 years and older - as compared to the early onset group. Is it because our clinicians are getting better at recognising MG, or is it because we are living older or is there another reason?
To investigate this finding researchers must first collect all the information possible and describe accurately the symptoms and signs that patients present to the hospital at the very first instance. The project hopes to contrast and compare both early onset and late onset and also to look at the different antibodies that can be detected in the blood samples to see if there is any difference in the immunological profiles. It hopes to assess their 'Quality of Life' data throughout follow-up.
Since the start of the study in August 2014, they have recruited 150 patients with MG and 8 patients with Lambert-Eaton myasthenic syndrome (LEMS) making this the largest prospective cohort study in MG to date with 100% recruitment rates in the Trent region and with other recruits from out of the region who volunteered to participate in the study. Three quarters of the patients are over 50 years of age with approximately half of the patients having purely ocular myasthenia at diagnosis.
The findings indicate that the older patients are also more likely to need inpatient hospital treatment. Nearly 95% of these patients have an antibody related to myasthenia in their blood.
In an extension of this project, Dr Sui Wong is recruiting patients directly from Moorfields Eye Hospital, who will therefore have a more ocular form of MG and she reports that recruitment to the project is continuing steadily as projected.
In Oxford, Professor Beeson and his student Mirela Panea are working on "Super Synapses". Over the last ten years Professor Beeson and his group, in studies partially funded by myaware, have been investigating how the transfer of information from nerves to muscle is impaired in myasthenia, how this results in muscle weakness and how it may be overcome. This project is now focussing on a protein at the nerve/muscle junction called DOK7, which is crucial for maintaining the correct structure of this junction and allows for the information to be efficiently passed from the nerve to the muscle. Recently, Professor Beeson's group have shown that if abnormally large amounts of the DOK7 protein are produced in muscles it causes the nerve/muscle junction to be greatly enlarged and these bigger of 'super' synapses are very efficient in transferring information. If there was a drug that could increase the amount of DOK7 in the, it would prove highly effective in treating most forms of the genetic myasthenic syndromes and might also be helpful in autoimmune myasthenia.
This project is being carried out with another group in Oxford University who have already used a similar strategy to identify drugs that do similar jobs in muscular dystrophy and are already at the clinical trials stage in that disease.
Victoria Selby from University College London, has been developing and validating specific home-based assessment tools for monitoring the fluctuations in fatigability and muscle performance in adult and paediatric patients with myasthenia. Current clinical services are designed to monitor disease progression and medical management but physical fluctuations in symptoms are rarely objectively measured. Additionally, clinic assessments are often spaced months or more apart and so ideally these assessments should be supplemented by a tool which can detect changes in functional ability at home. Victoria's study has involved qualitative research and assessment programs to identify the specific challenges people have to overcome when living with myasthenia. Adults and children (5-18 years) have taken part in semi-structered interviews and from this initial study, a further 17 adults and 7 children have been recruited to participate in the assessment of the home-based tool to assess daily and seasonal variation.
In the fifth project, due to be completed at the end of summer 2017, Dr Maria Farrugia and Caroline Carmichael of the West of Scotland Myasthenia Service have set up a pilot study to investigate a physical and psychological approach to improve fatigue in patients with myasthenia gravis. Ten patients were recruited who reported significant fatigue, rather than muscle fatigability, and in whom their myasthenia was felt to be relatively stable and so were unlikely to experience medication changes during the trial period. The trial involved one 10-week program looking at various lifestyle aspects which may influence/exacerbate fatigue. Each week a different aspect of their lifestyle was addressed with input from physiotherapy, neuropsychology and specialist nurses. The program has been completed and we look forward to the final assessment and report on this pilot study.
A recently completed myaware funded project, carried out in Southampton by Dr William Rae, Georgina Burke and Ashwin Pinto, has recently been published in the Journal of Neuroimmunology (2016) 293: 82-85. This is a study that analyses the breakdown products (metabolites) of azathioprine in the blood of patients with MG. Patients with troublesome symptoms of autoimmune myasthenia gravis are typically treated with medication that suppresses the immune system. Most patients take a combination of prednisolone (steroids) and other drugs, known as steroid-sparing agents. The most commonly prescribed steroid-sparing agent for treatment of myasthenia is azathioprine and the dose given is typically calculated according to the patient's weight. Recently, new biochemical blood tests have been developed to monitor patients on azathioprine and help to predict whether patients are on the correct dosage of azathioprine. Dr Pinto and colleagues studied 19 patients who had been taking azathioprine for over one year and found that new metabolite tests were helpful in adjusting the dose if patients had abnormal routine blood tests or suffered with frequent infections. In addition, some of the patients did not appear to benefit from azathioprine at the standard dose and the tests could help to decide whether an increase in dose would be effective for these patients. The results were also presented at the Specialist Interest Myasthenia Group at the Association of British Neurologist meeting in May 2016, and was very well received.
Myaware are committed not only to funding basic scientific research but also to producing neurologists in the future with a special interest and knowledge in myasthenia. Myaware has therefore recently asked for applicants for a new myaware Clinical Training Fellowship. This fellowship will enable the trainee to undertake a substantial research project related to myasthenia, and to a higher degree.