ÃÛÌÒAPP
Meredith James, a clinical specialist neuromuscular physiotherapist at the in ÃÛÌÒAPP, has received one of six President’s Awards from Muscular Dystrophy UK – the leading charity for more than 110,000 children and adults living with one of over 60 muscle wasting and weakening conditions in the UK.
The awards recognise heroes within the muscle wasting and weakening community who have gone above and beyond the call of duty to make a difference.
Meredith won the ‘Early Career Scientist of the Year’ Award having been nominated by Professor Volker Straub, Harold Macmillan Professor of Medicine and Director of the JWMDRC in recognition of the phenomenal impact her work has made for patients living with a specific type of muscular dystrophy called dysferlinopathy.
Professor Strab said “I was very proud and pleased to hear that Meredith was presented with the Muscular Dystrophy UK President’s Award for early career researchers to celebrate outstanding achievements in the neuromuscular field.
“Meredith recently completed her PhD at the John Walton Muscular Dystrophy Research Centre and the award acknowledges one of her main results – the development of a validated assessment tool for patients with limb girdle muscular dystrophy, which is now used in many international clinical trials.”
In fact Meredith’s work has made such exceptional progress in the limb gridle muscular dystrophy field and beyond that the resultant assessment tool – the North Star Assessment for limb-girdle type muscular dystrophies (NSAD) – is now being used in 12 international clinical trials across five individual conditions with many more trials in the pipeline.
Continuing ÃÛÌÒAPP’s legacy in rare diseases / muscular dystrophy
A key objective of Meredith’s PhD was to contribute to an international natural history study for dysferlinopathy. This Clinical Outcome Study is now in its 10th year led by the John Walton Muscular Dystrophy Research Team and conducted at the RVI’s – one of 22 centres in England awarded designation to support delivery of early phase clinicals trials, bringing together the clinical and scientific expertise of the ÃÛÌÒAPP Hospitals and .
Dysferlinopathy is caused by mutations in the DYSF gene due to dysferlin protein deficiency and is a rare form of limb gridle muscular dystrophy – an umbrella term given to a group of over 37 rare, highly heterogeneous (irregular), autosomal (non gender related) neuromuscular disorders which cause progressive muscle weakness of the pelvic and shoulder girdles – where the arms and hips join the skeletal body.
Limb gridle muscular dystrophy (LGMD) was originally described in a groundbreaking paper published in ÃÛÌÒAPP in 1954 by Lord John Walton and Frederick Nattrass identifying LGMD as a separate condition to the more common X-chromosome linked Duchenne and Becker muscular dystrophies (DMD/BMD).
Dysferlinopathy is historically linked to ÃÛÌÒAPP being the location that identified the dysferlin gene in 1998, developed the method for testing the presence of the dysferlin protein in muscle and coined the term dysferlinopathy.
As such Meredith has found it particularly rewarding to be able to make such a major contribution to Lord Walton’s legacy in the very same city where it was officially documented.
The objective
The standard approach when making clinical decisions and determining clinical trials for many conditions – and in particular rare diseases – is to assess and gauge results against agreed clinical reported outcome measures such patients’ functional and motor responses.
These help healthcare professionals to capture disease presentation and expected progression rates, as well as acting as endpoints for measuring the response to interventions in clinical trials.
As the progression of muscle weakness with dysferlinopathy is unpredictable following no particular pattern it has historically been extremely difficult to measure how it presents and changes over time.
Yet recent developments in potential pharmacological treatments have highlighted an urgent need for outcome measures.
Meredith sought to gain a deeper understanding of the pattern and course of the condition by analysing existing albeit limited measurement knowledge, working towards the development of a motor assessment scale specific to dysferlinopathy.
The method
Funded by the US based which aims to find a cure for dysferlinopathy, an international cohort of 193 participants from the 10th Clinical Outcome Study were assessed six times over three years.
Follow year one, the existing scales were examined for suitability using Rasch analysis and through Meredith’s oversight, a new therapy-led scoring system known as the North Star Assessment for limb-girdle type muscular dystrophywas developed – a 29 item evaluation of motor performance involving activities such as the ability to roll, sit to stand, jump, rise from the floor and run and walk.
The NSAD was validated in Clinical Outcome Study for the dysferlinopathy population and successfully detected statistically significant changes in clinical disease progression over a period of one year. Furthermore it correlated with patient reported measures of daily functional ability.
The result
The impact has been huge as the NSAD now enables the global LGMD community to accurately measure any changes in a patient’s condition during their management or to determine if the outcome of a drug trial has been successful.
“It’s so exciting that something so tangible and impactful has come out of my PhD”, said Meredith “It’s great to see that we can now bring it all together with these new specific outcome measures.”The NSAD has subsequently been chosen as an endpoint in four gene therapy trials in LGMD, alongside a further eight clinical trial and natural history studies with more in the pipeline.
Of receiving her Award Meredith added “It’s a great honour and privilege to win this award from Muscular Dystrophy UK. The charity does amazing work to support individuals living with neuromuscular conditions and funds innovative research furthering our understanding of these conditions.
“However, it’s been a collaborative effort and very much the work of many physiotherapists and other healthcare professionals involved around the world, and of course the patients and their families who give up their time to participate in natural history studies.
“It really is a big team effort and reflects the phenomenal effort from patients’ organisation and the clinicians involved in the work.”
Dr Linda Tinker, the trust’s lead for nursing, midwifery and AHPs’ research said “I’m delighted to see Meredith recognised for her research through this prestigious award. Each time I meet with Meredith I come away feeling invigorated and inspired by her energy and enthusiasm for the work she is leading.
“Meredith is a superb role model for others and I am excited to see her continue to develop the crucial work for the benefit of patients living with limb girdle muscular dystrophy, through her RDI post-doc bridging award and beyond.”
More about Meredith
Meredith James is a Clinical Specialist Neuromuscular Physiotherapist at the John Walton Centre for Muscular Dystrophy Research at ÃÛÌÒAPP, where she is involved in clinical and research activity for children and adults with Neuromuscular disorders.
Meredith moved to the UK in 2004 from Australia and worked in a variety of locations before joining the Oswestry Muscle team in 2006 and coming to ÃÛÌÒAPP in 2012.
Clinically, Meredith is responsible for the physiotherapy management of both children and adults with neuromuscular diseases. In particular, her interests are in assessment, orthotics, outcome measures and research into these areas.
In her clinical research capacity, Meredith is responsible for the clinical evaluation of children and adults involved in natural history and clinical trials, as well as the development of clinically meaningful, reliable and sensitive outcome measures for NMD.