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WDO Member Meeting 2019

The first WDO Member Meeting of 2019 was a great success. Over 50 participants from 24 countries gathered on February 15 in Rome to exchange experiences and learn about updates in the DMD field. In the morning there were two masterclasses on preclinical and clinical drug development by Prof. Dr. Annemieke Aartsma-Rus and Prof. Dr. Nathalie Goemans, followed by a presentation on endocrinology and bone health by Dr. Jarod Wong. The meeting was chaired by Prof. Dr. Eugenio Mercuri. In the afternoon, there were updates on ongoing projects and technical developments. 

Masterclasses on preclinical and clinical drug development

From the discussion that was chaired by Prof. Dr. Eugenio Mercuri, it is found to be imperative that Patient Organisations (PO’s) are a credible source of information on clinical trials and only support optimal trials. PO’s should not promote trials without checking with the experts and should boycott suboptimal trials. Also, it is not enough to show production of dystrophin, for example, but that this is functional. Proof of concept is necessary before going into clinical trials, and companies should go to Treat-NMD for a TACT review before planning clinical trials. POs can access TACT reports on the TREAT-NMD website for more information. One idea was to create a grid with specific questions, such as what is preclinical data and proof of concept, and create webinars on clinical trials for patients with a list of specific questions that need to be answered before patients enrol.

Endocrinology & Bone Health

Boys with DMD often struggle with poorer bone quality, due to bones being smaller and much thinner. This means that fractures occur more frequently: 50% of DMD patients have X-ray confirmed fractures. Dr. Jarod Wong presses the importance of always wearing a wheelchair seat belt to improve safety and prevent falling over. Bone density scans via DXA are not predictive of vertebral fractures; patients on steroids should have a lumbar X-ray at least every 2 years, and non-steroid users every 3 years.

Steroids are known to exacerbate osteoporosis in DMD, with boys on daily deflazacort demonstrating both the shortest time to a first vertebral fracture as well as the worst degree of growth failure. Steroids also lead to secondary adrenal insufficiency, resulting in short stature, delayed puberty, obesity (in some) and metabolic consequences. Things to look out for are Fat Embolism Syndrome (FES) after bone injuries; acute and chronic back pain are likely to result from vertebral fractures, although these can also be asymptomatic; progressive kyphosis and restrictive lung disease.

World Duchenne Awareness Day 2019 Theme

This year’s theme for World Duchenne Awareness Day is ‘Nutrition in DMD’. This not only covers guidelines for maintaining a healthy weight for DMD boys and families, but also aims to spark inspiration, and to encourage research in this field. Nicoletta Madia announces the theme and opens the conversation to determine the biggest challenges for nutrition.

In summary, the biggest challenges in nutrition can be divided into three categories:

  • Inspire children and their families to eat more healthily in an age-appropriate way, taking the psychological aspect into account
  • Educate families, clinicians, researchers and other healthcare providers on the importance of nutrition in DMD
  • Guidelines for supplements and how they might interact with medication

If you see anything missing or want to add on to these subjects, please contact Nicoletta Madia.

The Importance of Data Collection

Prof. Dr. Nathalie Goemans states there have been major therapeutic efforts over the past decade, but there have been issues with the design and interpretation of early clinical trials. Primarily scarcity of patients, an incomplete comprehension of the course of the disease, and a lack of Natural History (NH) data and inter-patient variability are are the base of this. By sharing data, dialogue with regulators to gain qualification from CHMP and harmonisation in IT support we can overcome the rare disease problem and empower trials.

Data sharing will provide better insight into outcome measures, improving trial design and enable more reliable stratification criteria. Furthermore, it will provide a benchmark for the clinical relevance of study results, and helps determine variability factors such as age/stage, Standard of Care and steroids, and genetic aspects. Pooling data will enable the analysis of larger data sets in collaboration with CTAP, e.g. trajectories of 6MWD, and help identify prognostic factors. This will help inform regulations and policies; NH data can be used to enrich the placebo arms, and it will play a role in post marketing surveillance.

10 Years of Connect and New Developments

After 10 years, the Connect registry technology is outdated and has been replaced by Duchenne Registry, to which a number of other components have been added:

  • PPMD PRO Platform THREAD Research, where studies using wearable devices can be done in the registry; exploratory and validated patient-relevant outcomes can be developed with academic and industry partners; and will be used by the 25 Certified Duchenne CARE Centers (CDCC) in the US
  • DORI, Duchenne Outcomes Research Interchange, (Partnering with Sarepta), which will combine data from the Duchenne Registry with patient-reported data, clinician reported data, electronic health records and post marketing surveillance data provided by industry partners with approved therapies

The data will be used to inform drug development, engage payers, inform regulators and empower the DMD community.

Duchenne Map

The aim of Duchenne Map, as presented by Dimitrios Athanasiou, is to connect the Duchenne world visibly, from patients, care centres, doctors, researchers, industry, to patient organization, and healthcare experts. It will enable clinical trial recruitment in a safe space as well as coordination and managing expectations. It will also prevent patients and patient organizations wasting valuable time on duplicating efforts in many different areas.

The next stage is getting input for the graphics and initiating the three tier validation process: on registration the user will be provided with a link, this will be approved (or not), and then permission will be given (or not) for the user to add information to the map. This validation process is essential to ensure the quality of the information provided in the map.

For more information about Duchenne Map, please contact [email protected].

Next Generation Data Sharing

Elizabeth Vroom states there is a lot of data out there in the world that needs bringing together, but what is the value for patients of sharing their data? There are a myriad of challenges when it comes to data sharing: you have interoperability, the GDPR, a lack of awareness of the advantages of data sharing, and the fear of giving away data, just to name a few. The lack of knowledge of new methodologies and initiatives to improve data sharing makes we are missing out on new developments, like the use of Artificial Intelligence (AI) the Personal Health Train and the rise of platforms that enables patients to ask their own questions, all according to FAIR principles: Findable, Accessible, Interoperable and Reusable.

DPP NL is currently working on the Duchenne Platform (Dutch link) for data collection and data sharing; the data will be stored in “lockers” – medical records, genetic information, phenotype, PROMs, care at home, education, data from wearables, “real world data”. Each participant decides who he shares what with and when. The data collected via this platform will also be relevant for regulatory and health technology assessment bodies, as well as for payers. To further enable this process, there will be an international meeting on data sharing in Amsterdam in March 2019.

Ongoing Projects on Assistive and Rehab Devices

Dr. Ir. Joan Lobo Prat and Dr. Mariska Janssen end the day with a presentation on rehabilitation devices. One example is that of Flextension: a technical solution to improve independence and quality of life in DMD.

During the “compensatory” phase, passive support is sufficient to enable a much wider, natural range of motion while compensating for the weight of one’s arms. The PUL will be used to evaluate its effectiveness. When active support becomes necessary, the device replaces the usual wheelchair arm support, and Flextension is working on alternative ways to move the arm support in the right dimensions, e.g. eye tracking. Another option is an hydraulic hand orthosis that increases grip strength (Symbi-Hand), or Shellmech to support the trunk. Furthermore, two head supports are being developed: one moves with the back rest, the other supports the rotating head. The arm support to compensate loss of arm function will soon be available.

More information

For more information about the WDO Member meeting, and a request to receive the slides of the presenters (if available), please contact Suzie-Ann Bakker.