Recently published in The Lancet Neurology, a new Policy View written by Volker Straub and colleagues outlines the collaborative effort of stakeholders in Duchenne muscular dystrophy (DMD) to accelerate the development of treatments, suggesting it may serve as a paradigm for other rare diseases. Developing therapies for genetic diseases poses unique challenges, as shown by the example of DMD - a rare, progressive, muscle-wasting disease affecting about one in 5000 newborn boys. Only one DMD therapy (Ataluren) is currently available, and is only applicable to 13% of patients, with others in development.

The requirements essential for regulatory approval of any new treatment, such as comprehensive data from natural history, and meaningful outcome measures assessing clinical benefit, are not always in place when potential therapies enter the clinical trial phase. The cooperative effort of stakeholders in DMD, including patients’ groups, academia, industry, and regulators, aimed to address this shortfall by identifying strategies to overcome challenges and collecting relevant data.

In an interview on The Lancet Neurology Podcast, authors Elizabeth Vroom and Annemieke Aartsma-Rus discuss the reasons behind the article and what it hopes to achieve. The Duchenne field endured a steep learning curve over the past decade, as the first potential treatments began to enter clinical trials. This next stage required new tools and additional data in order to further drive drug development, with DMD stakeholders having to work together to proceed. The Policy View describes the process: 'the journey we went through to get to where we are now, because this same route will need to be taken by other rare diseases' states Annemieke.

The article suggests functional and molecular outcome measures should be developed in collaboration with patients’ representatives and regulators in order to stimulate and assist orphan medicine development. High-quality data for natural history and outcome measures are crucial for clinical trial design and regulatory approval; ideally, data should be obtained before or in parallel with potential treatments.

Straub, Volker et al. "Stakeholder Cooperation To Overcome Challenges In Orphan Medicine Development: The Example Of Duchenne Muscular Dystrophy". The Lancet Neurology 15.8 (2016)

TREAT-NMD Executive member Matthew Wood has chosen to step down from his role on the committee. We would like to thank him for his contribution to the Executive Committee and the wider neuromuscular community.

This leaves an Academic vacancy on the Executive Committee. Executive Committee members provide guidance to the secretariat and drive forward the TREAT-NMD workplan. Meetings are monthly most via a teleconference, with an annual face-to-face meeting. Any nominations should be sent to Stephen Lynn before the 31st August 2016.

Voting will take place in early September and the successful candidate announced mid-September.

1. New mode of inheritance for Limb-Girdle Muscular Dystrophy Type 2A

The term limb girdle muscular dystrophy (LGMD) encompasses a collection of muscular dystrophies sharing common clinical features such as weakness and atrophy of proximal ‘limb girdle’ muscles. The most widespread form worldwide, LGMD type 2A, is caused by mutations in the calpain 3 gene (CAPN3). Previously, it was assumed that both alleles of CAPN3 must be mutated to cause calpainopathy. However, a new report by Vissing and colleagues provides strong evidence that LGMD2A also exists in dominantly inherited form.

Three patients from three families, previously seen as sporadic cases, were revealed to carry a single, 21-basepair deletion within CAP3N - causative of a form of LGMD2A. Researchers in the UK, Sweden and Norway have since found families carrying the same single-gene mutation. The Brain article describes the new mode of inheritance and suggests how it may impact diagnosis and treatment.

Vissing, John et al. "A Heterozygous 21-Bp Deletion Incapn3causes Dominantly Inherited Limb Girdle Muscular Dystrophy". Brain (2016)

2. MYO9A mutations identified in Congenital Myasthenic Syndrome

Dysregulation of the neuromuscular junction, a specialised synapse critical in muscle contraction, can lead to Congenital Myasthenic Syndrome (CMS): an umbrella term comprising a group of rare and varied muscle-weakening disorders commonly affecting chewing, swallowing and movement of the eyes. Despite over 20 causative genes being identified, around a fifth of those diagnosed with CMS lack a genetic diagnosis - suggesting contributing genes still remain to be revealed.

A new 'Brain' article by O'Connor and colleagues suggests mutations in the MYO9A gene are causative of CMS. The unconventional myosin MYO9A functions at the neuromuscular junction, and mutations of the MYO9A gene are associated with CMS in two families. Their findings highlight the need to look outside traditional neuromuscular junction-specific proteins for further CMS candidate genes.

O’Connor, Emily et al. "Identification Of Mutations In Themyo9agene In Patients With Congenital Myasthenic Syndrome". Brain (2016)

The Swedish 'Collection Foundation for Muscular Dystrophy Research' (SMDF) is a non-profit foundation that works to raise money to fund research in Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). SMDF is actively working to disseminate information on diagnoses and support families, professionals and others who work and come into contact with people with DMD and BMD. As part of their work, SMDF organizes a symposium every two years for all in order to provide information on the state of research, treatment programs and other relevant topics.

Videos of presentations that took place at the SMDF 2016 Symposium for Duchenne and Becker Muscle Dystrophy in Gothenburg, Sweden in April are now available online. Alongside talks given in Swedish, topics covered in English include 'An active life for all' with Magnus Lindwall, Henrik Petrén and Ann-Louise Peterson and 'Growing up with Muscular Dystrophy' by Imelda de Groot.

A music video created by and starring boys with Duchenne muscular dystrophy (DMD) was produced as part of a promotional film project by the German Duchenne Foundation in Hamburg. Written and rapped by Noh Gourie, Tobias Kozlowski and friends, 'Never Forget Duchenne' describes their experiences of disability and gives encouragement to all Duchenne sufferers worldwide. The song aims to increase public awareness of DMD as well as the Action Benni & Co Foundation.

Founded in 1996 by a family whose son Benni suffers from DMD, the Foundation aims to; accelerate research into developing treatments; allow families affected by DMD to share their experiences and spread awareness of Duchenne through social projects, such as this one. The current Ü16 public relations project was possible thanks to proceeds from the Action Benni & Co Charity Run in 2015.

Watch the video here

The Global FKRP Registry has released its sixth newsletter and it is available to download from the registry website. The newsletters are lay friendly and used as a way to inform patients and families, as well as doctors, about what is going on with the registry and anything else FKRP-related.

Some highlights of this issue:

Registry data – some data from the registry is presented, highlighting that there are 451 patients registered, with 210 of them being genetically confirmed as having an FKRP-related condition – the largest known cohort of genetically confirmed FKRP patients.

Patient stories – there is one new patient story available to read in the newsletter and it is also available on the registry website in the library of patients’ stories.

Research updates – in this section an update on further work on mouse models for FKRP, a publication about the cardiac involvement in patients with limb girdle type 2, and a new potential function of FKRP in the glycosylation process are presented.

International collaboration and trial readiness for LGMDs – this section highlights two European Neuromuscular Centre (ENMC) workshops: one looking at the clinical trial readiness for FKRP related muscular dystrophies and the other one dedicated to the dystroglycan and the dystroglycanopathies. Additionally, two recent publications on international collaborations and clinical trial readiness for limb girdle muscular dystrophies are presented.

See all of the newsletter on the Global FKRP Registry website.

For more information on the Global FKRP Registry, including how to participate, contact [email protected].

Please tell us about your role /organisation / background

I am a paediatrician and I am currently the Head of the Neuromuscular Reference Centre University hospital in Leuven. I am involved in supporting many clinical trials.

I feel fortunate to have had such an interesting career. I began as a child neurologist. When I was working in Leuven in 1987 I was asked to develop a neuromuscular programme and I established a multidisciplinary team. I was spoilt working in Leuven due to the location of the clinicians and facilities.

I began in neuromuscular diseases (NMD) at a really good time, and had the opportunity to create standards of care and new diagnoses. It was a really exciting area as new genetic diagnosis developed. Later there were therapeutic strategies. I feel lucky to be in the field in a time frame with such interesting developments

How did you become a TREAT-NMD Executive Committee member, and what does the role involve?

As I have been involved with NMD for a long time, and I am very active in the field it was important to get involved. TREAT-NMD is crucial to improve translational research, standards of care and outcome measures. I have seen the field growing so much, TREAT-NMD has had an important role in this especially with research, care and treatment.

I am currently also the chair-elect of the TREAT-NMD Global Database Oversight Committee (TGDOC). Registries are so important for clinical research and developing standards of care; is important to increase thieir coverage and the data quality of the global registries. I am excited to take on this challenge, and play a role in their development.

I like the way there is different expertise within the Executive Committee – I bring experience from clinical aspects and my experience with regulatory authorities. I am committed to representing TREAT-NMD.

What do you see as the biggest challenge to the neuromuscular field (in relation to translational research?)

To keeping working together – this started well but it gets more complex as it grows.

The partnership with industry is needed and accelerates the drug access, but it is complex. We have learnt a lot recently it is a long road, but not a straight road! There have been recent disappointments but we are stronger in communicating and supporting patients through these times.

Why is TREAT-NMD so important for the field and why should people become a member?

We need each other! We are stronger together.

Tell us something about yourself that not many people will know?

I am an open book so most people know me! I like music and dancing. I have three (and a half) grandchildren which bring me joy!

14th International Congress on Neuromuscular Diseases. 5 - 9 July. Toronto, Canada.

The 14th International Congress on Neuromuscular Diseases will include sessions on muscular dystrophies, other myopathies, myasthenia gravis, polyneuropathies, spinal cord disorders, and neurofibromatosis to name some of the major themes within the Congress. There will also be updates on understanding of the genetics, pathogenesis, evaluation and treatment of neuromuscular disorders. At the end of this Congress, it is hoped that attendees feel that they have garnered the most up-to-date information available in neuromuscular disorders.

Registration is now open for two important Rare Disease (RD) events, both to be held at the National Centre for Rare Diseases, Istituto Superiore di Sanità, via Giano della Bella, Rome, Italy in September 2016:

"4th International Summer School on Rare Disease and Orphan Drug Registries"

September 26-28, 2016

The Summer School will consist of plenary presentations and interactive small-group exercises, according to the Problem-Based Learning methodology. The course will provide participants with useful tools and methodologies to establish, manage and plan the activities of a patient registry with an overview of new approaches.

"RD-Connect BYOD Workshop to Link Rare Disease Registries"

September 29-30, 2016

The Bring Your Own Data Workshop will be a hands-on experience, where the attendees work with FAIR (Findable, Accessible, Interoperable and Reusable) data experts to make their (sample) data FAIR and linked to other data that has been made FAIR before. The workshop will consist of preparatory webinars (one as a presentation at the Summer School), brief plenary introductions and practical working groups where participants see practically how to make their data FAIR and linkable, link it with other linkable data and see how easy it becomes to answer difficult queries.

Both events are open to health professionals, researchers, medical specialists, medical students, registries curators, database managers and representatives of patient associations, who are involved in or intend to establish a rare disease patient registry. A selection process will be applied based on the participant’s background and role with reference to registry activities.

Registration for either event is carried out by filling the on-line form before the deadline of July 10, 2016.

The Cure SMA annual conference took place over the weekend of the 16th of June in the USA. It is the largest SMA conference in the world. The conference brings together researchers, healthcare professionals, and families to network, learn, and collaborate. The family conference includes a variety of workshops, keynote sessions with leading researchers, a family-friendly research poster session, and more—plus fun events like a pyjama party and movie night, and teen and adult social activities.

The ultimate goal in drug development is to get treatments approved for as many people as possible, as quickly as possible. To help families understand this complex process, this year’s Annual SMA Conference included several presentations on clinical trials, the new drug access process, and issues that will impact access to a drug after it is approved, including insurance coverage and drug labeling.

The presentations from the conference can be accessed here.

The 2016 Annual SMA Conference was a huge success! Over the course of four days, many incredible memories were made. Cure SMA would like to thank all of the attendees for making this year so memorable!

The 26th June saw a range of stakeholders descend on the British Library in London to attend the "Making Outcomes Work - Stakeholder Workshop on outcome measure development and implementation for DMD" workshop chaired by Volker Straub and Andrew Blamire. More than 70 clinicians, researchers, industry representatives and patient organizations attended the workshop which was organized by SCOPE-DMD and BIOIMAGE-NMD, two FP7 funded projects both coordinated by Newcastle University, in close cooperation with the COST Action BM1207 on exon skipping, led by Annemieke Aartsma-Rus.

The “Making Outcomes Work” workshop followed the successful meeting on exon-skipping therapy development for DMD meeting held in London in April 2015.

The workshop focused on ongoing activities and advances in outcome measure development, focusing in particular on MRI, upper limb function and molecular biomarkers. The afternoon began with a focus on molecular biomarkers, with Pietro Spitali and Pierre Carlier presenting an overview of current state of play within imaging and molecular biomarkers. Maria Isaac from the European Medicines Agency then gave the regulators view on molecular biomarkers, followed by a panel discussion and questions from the audience. The second session focused on upper limb assessments with Michelle Eagle, Laurent Servais and Jean-Yves Hogrel discussing upper limb assessments. Elizabeth Vroom closed the session by discussing the importance of patient involvement in upper limb scale development, followed by a second panel and audience discussion.

Annemieke Aartsma-Rus closed the workshop by giving a future perspective and summarizing the discussions and different points of view from the day.

The annual Myotonic Dystrophy Support Group (MDSG) conference was held on 25th June in Nottingham, UK. This annual event attracted more than 200 people from across the country and gave patients with myotonic dystrophy and their families the chance to share their stories and experiences, as well as hear about up to date research and participate in workshops.

The day started with invited speakers Professor David Brook, from the University of Nottingham, who discussed the exciting developments in his lab and the progress being made thanks to a recent Wellcome Trust Award. Dr Tetsuo Ashizawa visiting from the University of Florida provided an overview of myotonic dystrophy and some insight into the research on-going in the United States.

Patients were excited to hear about the phase I/II clinical trial sponsored by IONIS that is currently reviewing results. Dr Nikoletta Nikolenko speaking on behalf of Professor Lochmϋller from John Walton Muscular Dystrophy Research Centre, Newcastle, presented an overview of the clinical research being carried out at the centre, including the OPTIMISITC trial sponsored by the European Commission and natural history study PHENODM1 sponsored by NIHR.

This was followed by three sessions of workshops covering research as well as a range of medical and social issues. The final session of the day included a moving presentation from Mr Erich Maurer, who, inspired by Margaret Bowler has set up a support group in Switzerland. For more information about the Myotonic Dystrophy Support Group see their website.

SOLANE (Latin American Society of Neuromuscular Diseases) is proud to announce the first Latin American Symposium to be held on September 9 – 10 in Buenos Aires, Argentina.

SOLANE is an old dream that is starting to thrive, a dream in which we have been working with great effort since 2011. SOLANE aims to become an international Organization bringing together leading specialists, patient organizations and industry representatives to ensure the best practice in neuromuscular diseases treatment. That is the goal we wish to meet.

In such an extensive region like LATAM, where 650 million people live, the field of Neuromuscular Diseases is barely developed. Thus far, there are just a few specialized centres and access to an accurate and timely diagnosis is almost impossible for most patients. By recognizing and sharing our clinical understanding among the region we expect to create a strong regional network to revolutionize how patients are being managed. Thus, our first and foremost aim is to foster our learning in neuromuscular diseases and our scientific and clinical understanding, so that we can work collectively as a region towards improving patient outcomes.

In our web page, it can be seen that a great number of Latin American colleagues as well as professionals from Europe and USA have accompanied us in such an endeavour. We are honoured to count on such distinguished professionals who form part of our Scientific Committee and Honorary Board.

SOLANE’s Symposium will be the first Latin American meeting ever held concerning Neuromuscular Diseases

More details of the Symposium can be found through our website