30th September 2016
Cellular Mechanism Discovery for SMA

A team of scientists led by Brunhilde Wirth from the Institute of Human Genetics, University of Cologne, Germany have uncovered cellular mechanisms that may lead to new therapeutic strategies for the treatment of spinal muscular atrophy (SMA). The research which has been published in the prestigious American Journal of Human Genetics, can be read here.

SMA is a genetic disorder that affects the motor neurons of the nervous system controlling the muscle movement, and is the most common inherited cause of death in children under the age of 2.

The study made use of an existing striking finding related to SMA protective modifiers to unravel the cellular mechanism disrupted in SMA. In this study, the scientists investigated the underlying cause of endocytosis impairment in SMA. Endocytosis is a form of active transport in which a cell transports molecules (such as proteins) into the cell by engulfing them in an energy-using process. This process is particularly important in neurons, to allow rapid release of neurotransmitters, which are messenger molecules.

The team of scientists were able to demonstrate that treatment with suboptimal survival motor neuron (SMN) antisense oligonucleotide combined with increasing the levels of two genetic modifiers, (Plastin 3 and Coronin1C) rescued survival (from 14 to >250 days) in a severe SMA mouse model.

The scientists therefore propose that the disturbance of endocytosis, is a key cause of impaired neurotransmission and neuromuscular junction maintenance, which may be a key cellular mechanism in SMA.

This research identifies a new and potentially exciting future combinational therapy. Altering levels of molecules involved in endocytosis could be used in conjunction with SMN-enhancing agents as a potential therapy for SMA.

FDA Grants Accelerated Approval to First Drug for
Duchenne Muscular Dystrophy
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The U.S. Food and Drug Administration (FDA) have approved Exondys 51 (eteplirsen) injection, the first drug approved to treat patients with Duchenne muscular dystrophy (DMD). Exondys 51 is specifically indicated for patients who have a confirmed mutation of the dystrophin gene amenable to exon 51 skipping, which affects about 13 percent of the population with DMD.

Exondys 51 was approved under the accelerated approval pathway, which provides for the approval of drugs that treat serious or life-threatening diseases and generally provide a meaningful advantage over existing treatments. Approval under this pathway can be based on adequate and well-controlled studies showing the drug has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit to patients (how a patient feels or functions or whether they survive). This pathway provides earlier patient access to promising new drugs while the company conducts clinical trials to verify the predicted clinical benefit.

The accelerated approval of Exondys 51 is based on the surrogate endpoint of dystrophin increase in skeletal muscle observed in some Exondys 51-treated patients. The FDA has concluded that the data submitted by the applicant demonstrated an increase in dystrophin production, that is reasonably likely to predict clinical benefit in some patients with DMD who have a confirmed mutation of the dystrophin gene amenable to exon 51 skipping. A clinical benefit of Exondys 51, including improved motor function, has not been established.

The FDA granted Exondys 51 fast track designation, which is a designation to facilitate the development and expedite the review of drugs that are intended to treat serious conditions and that demonstrate the potential to address an unmet medical need. It was also granted priority review and orphan drug designation.

Limb Girdle Awareness Day (TODAY!)
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The second annual Global “Limb Girdle Muscular Dystrophy Awareness Day” will be held on September 30th 2016. The goal is to globally draw attention to this group of rare neuro-muscular diseases which can impact the lives of many from childhood through adulthood, as LGMD occurs in all parts of the world and among all ethnic groups. Further details about this can be found here.

One of the resources for the LGMD community are patient registries. More information on LGMD related registries can be found on the TREAT-NMD website here.

TREAT-NMD Alliance Executive Committee Welcomes
New Academic Member
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The TREAT-NMD Alliance Executive Committee is pleased to announce the election of a new academic member, who is replacing Matthew Wood on the committee.

Dr J. Andoni Urtizberea has been duly elected to the Executive Committee. He is currently a consultant at the Hendaye Hospital in the French Basque region, which is part of the large Assistance Publique - Hôpitaux de Paris (AP-HP) hospitals group and Deputy Coordinator of the French Neuromuscular Network, FILNEMUS. Andoni has also led the annual Summer School of Myology in Paris for the last 19 years. On behalf of the TREAT-NMD Alliance we want to thank all candidates for their interest in becoming a member of the Executive Committee. All candidates were of excellent quality and all received substantial votes. We hope they will continue to support the activities of the TREAT-NMD Alliance in the future.

Changes to TGDOC Committee
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There are changes to the TREAT-NMD Global Database Oversight Committee (TGDOC) following endorsement at the annual meeting (which took place in Leuven earlier this month). Nathalie Goemans took over as Chair from Hugh Dawkins (Hugh remains in the troika as Outgoing Chair) Craig Cambell takes over as Chair Elect. Jan Verschuuren will remain in an advisory role.

TREAT-NMD would like to thank all of the committee for their contribution and commitment to TGDOC. It was also agreed to make small changes to the charter to reflect the changes in the way data is provided, and the structure of TGDOC has been adapted to include disease specific sub-groups. The meeting was really successful and a full report will be available from the secretariat soon.

The Clinical Outcome Study for Dysferlinopathy
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The Clinical Outcome Study for Dysferlinopathy is a large international multicentre natural history study that recruited 209 participants at 15 different sites. The study is supported by the Jain Foundation and the first paper has been published from this study. This paper is a cross-sectional analysis of 193 patients derived from the baseline clinical and functional assessments. This ongoing longitudinal study will provide an opportunity to further understand patterns and variability in disease progression and form the basis for trial design.

The paper can be downloaded here.

The paper was also positively reviewed in the context of researching rare diseases in the same issue.

C3 Announces RFA to Fund LGMD2A
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Research Coalition to Cure Calpain 3 (C3) is excited to announce that we are actively soliciting research proposals.

The goal of this program is to provide funding support for projects that are likely to expand the understanding of calpain 3 and limb girdle muscular dystrophy type 2A (LGMD2A), also known as calpainopathy. This type of research will move us toward our ultimate goal of identifying a therapeutic approach for this disease. This award is not limited to US-based institutions. This award should not be used for indirect costs and overhead charges.

Applicants are encouraged to consult with C3 Scientific Director Dr. Jennifer Levy before submission of their proposal. Please see full program announcement. We encourage you to share this announcement with members of the research community.

The full program announcement can be found here:

C3 was founded in October 2010 to fulfill a mission to fund high potential research and clinical trials while educating the global community about the muscle-wasting disease LGMD2A (limb girdle muscular dystrophy type 2A), also known as calpainopathy.

Myotubular Trust - Seventh Call for Projects
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The Myotubular Trust was set up in 2006 to raise money for research to find a cure and or treatment for myotubular myopathy. There are three genetically distinct forms of Myotubular Myopathy, the commonest is x-linked, affecting only boys, and is also the most severe. This form usually presents in the new-born period and there are associated breathing and swallowing difficulties in addition to the general muscle weakness. The other forms are either dominant or recessive in inheritance and are usually milder and vary widely.

Seventh call for projects

The call for applications is open and the closing date for completed applications is Wednesday 30th November 2016. We anticipate making awards in May / June 2017. We are looking to fund further projects that will help find a cure and /or a treatment for any of the three types of myotubular myopathy (congenital X-linked recessive; congenital autosomal recessive; autosomal dominant), focusing on research that would not generally be funded by public or industrial funding sources. This call will be open to research bodies internationally.

We will be looking for the following types of application:

1.      A project grant applied for by a Principal Investigator to fund a project for 2-3 years duration to be carried out by a Post-Doctoral researcher, or PHD student

2.      A Myotubular Trust fellowship – basic science (3-4 years duration), where the scientist has identified a group that he or she wants to work with. Award is made to a named individual.

In particular, we would like to encourage the application of new technologies to research into myotubular myopathy, which may involve collaboration between different medical disciplines and / or different research institutions.

SMA Europe Call for Research Proposals
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Spinal Muscular Atrophy (SMA) Europe's 9th Call for SMA Research Proposals is now open.

This new International Call for SMA projects is open to any research project aimed at finding a therapy for SMA or at elucidating the basic pathophysiological processes of the diseases.

Priority will, however, be given to projects concentrating on the following areas:

  1. Understanding and Function of the SMN Complex and possibly other
  2. Factors, independent of SMN, as it relates to the pathophysiology of SMA
  3. Innovative approaches for therapy of SMA, including targeting non-SMN pathways
  4. Projects addressing bottlenecks impairing rapid translation from basic research to clinical trials, including (a) Innovative outcome measures & endpoints and (b) Appropriate methodology to follow disease progression and treatment effect
  5. The Natural History of SMA

To find out more about the Call, the eligibility criteria and how to apply, please read the launch document. To access the application portal (hosted by AFM Téléthon), please click here (and follow “SMA Europe 9th Call for Proposals”). The deadline for applications is 8th December 2016.

DMD Online Family Guide Now Available in 15 Languages.
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The online Duchenne muscular dystrophy (DMD) family guide summarises the results of an international consensus on the medical care of DMD.

This effort was supported by the US Centers for Disease Control and Prevention (CDC), in collaboration with patient advocacy groups and the TREAT-NMD network.

The main document is published in Lancet Neurology.

The information is now available in 15 languages. Hebrew and Chinese are the latest editions.

Slovene Version of the Standards of Care for SMA Now Available
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The SMA care guide for families and their doctors is now available to download in Slovenian (as well as a number of different languages). Translations into adittional languages are currently being prepared and will be made available here once they are complete.

If you feel a language should be included and you are willing to volunteer to translate all or some of the family guide please contact Becca Leary in the TREAT-NMD office in Newcastle for further details.

Stakeholder Meeting on Spinal Muscular Atrophy
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SMA Europe, TREAT-NMD, and the European Medicines Agency (EMA) are co-organising a one-day workshop on spinal muscular atrophy (SMA) on 11th November this year. The workshop will bring together key stakeholders (patient representatives, academics, industry and regulators) to discuss, help and advance the development of therapies for the treatment of SMA. Topics for discussion will include an overview of the disease, the pharmacology of the molecules under investigation, natural history data, clinical outcome measures and biomarkers. The meeting is by invitation only, but video streaming via the web will be available. The meeting is modelled after a similar stakeholder workshop on DMD that took place at EMA last year (see here for a free copy of a recent paper on stakeholder collaboration for DMD).

TREAT-NMD: Expert Masterclass on Duchenne Muscular
Dystrophy (DMD)
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Following the success of the first masterclass in 2015, this year’s two-day expert masterclass was held in Warsaw, Poland on the 8-9th September. The masterclass provided a high-quality scientific and educational meeting for paediatric neurologists and people involved in diagnosing and/or managing the care of patients with DMD.

The masterclass attracted 50 delegates from across 27 countries. The masterclass started with a presentation from Filippo Bucella (Duchenne Parent Project Onlus, Italy) who shared the experiences of families with DMD. Additional presentations were given by Academic experts, including a review of the current understanding of the natural history of DMD and best practice for the management of patients at various stages of ambulation and non-ambulation. Experts also provided updates on therapeutic advances in DMD and potential implications for clinical practice.

The masterclass format further included interactive workshops, which provided the opportunity for attendees to discuss methodologies for the evaluation of treatment outcomes, as well as discuss the regional differences and challenges in the diagnosis and management of DMD patients.

Finally, Elizabeth Vroom (Duchenne Parent Project Netherlands and United Parent Project Muscular Dystrophy) provided an overview of the support patient advocacy groups provide families of DMD patients, as well as the important role they play in helping DMD patients gain better access to DMD treatment.

TREAT-NMD received an unrestricted educational grant from PTC Therapeutics International Ltd for the organisation of this meeting.

International GNE Myopathy Registry Newsletter
5th Edition Now Available
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The International GNE Myopathy Disease Monitoring Program (GNEM-DMP) registry has released its fifth newsletter and it is available to download from the registry website.  The newsletter is used as a way of informing patients and families, as well as doctors, about what is going on with the registry as well as containing updates from the study partner on anything else related to GNE Myopathy.

This fourth issue contains the following articles:

  • Completion of Enrolment of the Phase 3 Ace-ER (Aceneuramic Acid Extended Release) Clinical Trial
  • GNEM-DMP Registry Update
  • GNE myopathy Patient Advocacy Event - Update of Days Events
  • Patient Advocacy at Ultragenyx
  • Launch of New Website
  • Patient Advocacy Summit: "Let's Talk Myopathy" - Barcelona, Spain
  • Remudy - Registry of Muscular Dystrophies (Japan)
  • Participant Story: ‘My Journey So Far’ – Yuriko Oda

See all of our previous newsletters on the International GNE Myopathy Registry.
For more information on the GNEM-DMP Registry, including how to participate please get in touch.

Global FKRP Registry 6th newsletter available now in
French and German
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The sixth issue of Global FKRP Registry is now available in French and German. The translated versions of the newsletter can be downloaded from the registry website. The newsletter aims to inform patients, families and clinicians about what is going on with the registry and anything else FKRP-related. See all the newsletters published to date on the Global FKRP Registry website. For more information on the Global FKRP Registry, including how to participate, contact us.

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The 15th Annual Kings Neuromuscular Disease Symposium. Friday 27th January 2017, London

The symposium will be held at King's College Hospital campus at Denmark Hill, in the stunning contemporary surroundings of the new Fetal Medicine Research Institute in London.

This annual educational meeting, organised by Dr Robert Hadden, is aimed primarily at clinicians who treat patients with diseases of the peripheral nervous system and muscle. This year's symposium aims to provide more practical general clinical review talks. It will be of interest to general adult neurologists, clinical neurophysiologists, paediatric neurologists, clinical neuroscientists, allied health professionals and trainees. It aims to provide a clinical update as well as an introduction to the science underlying neuromuscular diseases.

Further information here.

European Paediatrics Neurology Society (EPNS) Training Couse. 3rd-7th April 2017, Budapest

The EPNS has been organising training courses in paediatric neurology since 2003, specifically aimed at trainees but also at qualified paediatric neurologists who want to refresh their knowledge on certain topics. The aim is to cover most main topics in the syllabus over a three-year cycle and to promote contact between individuals in the speciality in different parts of Europe. The course has a highly interactive character and participants are encouraged to bring (difficult) cases to discuss. The number of participants is limited and applicants who wish to attend both courses will be given priority over those who wish to attend one of the two courses. The current cycle of training courses (2015-2017) is taking place in the beautiful city of Budapest, Hungary.

Futher information here.

Save the Date. Imaging in Neuromuscular Disease 2017 - First International Conference on Imaging in Neuromuscular Disease-

November 22-24, 2017, Berlin, Germany

The conference programme will feature internationally-recognized invited speakers highlighting developments and advances in all aspects of muscle imaging with sessions which will include: Diagnostic Muscle Imaging - New Imaging Techniques - Quantitative Muscle Imaging

Young researchers and trainees are encouraged to attend and participate. Selected abstracts will be featured for platform presentation during the sessions and all posters are eligible for poster awards. Further programme information and registration information will be available shortly via the MYO-MRI website.

Job Opportunity
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Clinical Research Fellow - Ref:1572209

UCL Department / Division: Institute of Child Health

Grade: CL7Salary: (inclusive of London allowance) £34,562 – £43,038 per annum, depending on skills and experience

The Dubowitz Neuromuscular Centre follows a large number of children affected by a variety of neuromuscular disorders.

The Centre is engaged in research focused on the genetic basis of the neuromuscular conditions and in translational research especially in congenital dystrophies, Duchenne muscular dystrophy and spinal muscular atrophy. This post offers an exciting opportunity for candidates seeking to carry out research in neuromuscular diseases within an established national centre of excellence. Research will be focused on genetic determinants of clinical severity for Duchenne and Becker muscular dystrophies and Spinal Muscular Atrophy. This post is funded for 31 months in the first instance.

The post is suitable for paediatricians; paediatric neurologists and geneticists interested in neuromuscular disorders. Applicants must be medically qualified with current GMC registration. Experience in neuromuscular disorders is desirable but not essential. Experience of initiating papers and abstracts for conferences and to present material arising from the research are essential to the post. The ability to carry out independent scientific work to a high standard is desirable.

30th September 2016
TREAT-NMD newsletter - 30th Sept 2016