DMD research

Duchenne UK attends the World Muscle Society 2018 Conference

Dr David Bull, Duchenne UK’s Director of Research, attended the World Muscle Society (WMS) Congress 2018 in Mendoza, Argentina earlier this month. WMS is an annual congress on neuromuscular disorders, it is attended by physicians, research scientists, therapists and neuropathologists from all over the world.

David headed off to Mendoza for a busy week meeting with other DMD patient groups from around the globe, as well as researchers Duchenne UK already work with and with other groups to discuss potential new projects for Duchenne UK to fund. David also attended many of the expert led presentations and seminars.

David Bull and Laura Della Pazze (Charley's Fund)

David Bull: “Being at WMS in Mendoza was a wonderful opportunity to catch up with friends from patient organisations around the world. As a result, we are now in touch with a PO in Turkey and are trying to help them as they develop their support networks for DMD boys and families. Also, the opportunity to hear about new lines of research and to talk to the scientists developing them offers us a chance to help make a difference to treatments for DMD. Next year, in Copenhagen, we hope to have a stand partnering with PPMD to encourage scientists to bring their ideas to us for support.”

Sarepta Seminar

One of the most exciting sessions for the DMD community was a seminar run by Sarepta. Sarepta therapeutics have a number of programmes under development for the treatment of DMD.

To start, Gilmour O’Neil (Sarepta’s Chief Medical Officer) gave an overview of their approach to tackling DMD, which focus on three areas: RNA target therapies (primarily exon skipping), Gene therapies (microdystrophin delivery) and Gene editing (CRISPR-Cas9).

Craig MacDonald then gave an update on Sarepta’s exon skipping programmes, focusing on three therapies, Exondys 51 (Eteplirsen), Golodirsen and Casimersen. Exondys 51 is the most advanced of these programmes, having been granted market authorisation in the US by the FDA in 2016. McDonald highlighted the positive pulmonary effects of Exondys 51, which has been shown to decrease rate of decline by a huge 50%.

McDonald then discussed Sarepta’s PPMO programme, which uses the addition of peptide chains to exon skipping therapies to improve the selectiveness and access of the exon skipping therapy. The PPMO programme for Exondys 51, Golodirsen and Casimersen are all doing well, the Exondys 51 PPMO is now undergoing a phase 1 clinical trial. 

Louise Rodino-Klpac, Sareptas Head of Gene Therapy, provided a potted history of microdystrophin gene therapy and an overview of the pre-clinical data Sarepta gathered for their AAV-microdystrophin programme.   

Perhaps the most highly anticipated moment was when Dr Jerry Mendel presented the latest data from the first four boys dosed in Sarepta’s microdystrophin clinical trial.

To summarise:

  • All 4 boys doing well
  • Biomarkers for CK and dystrophin show huge effects at 3 months
  • Early results show boys doing well
  • Good safety profile

You can read Sarepta’s letter to the community about this data here. It is important to remember that, although these results are exciting, only 4 patients have been dosed so far and we do need a larger sample size to confirm the effects of this treatment.

Duchenne muscular dystrophy treatments: Eugenio Mercuri

In this session Dr Eugenio Mercuri provided an overview of every form of treatment for DMD. A huge task, which he took on in just 40 minutes.

The therapies were split into three categories: substituting, correcting or ameliorating the primary protein defect (treating DMD symptoms), studies directly impacting the protein/restoring the protein and gene therapy (correcting/replacing the faulty gene). Many treatments were discussed but below a few are summarised.

Symptomatic treatments 

  • Reviewed use of steroids:
    • Rapid onset of effect and high impact
    • Regimen: start as soon as possible and continue past loss of ambulation
    • Dr Mercuri said there was no consensus as to whether it’s best to dose daily or intermittently. He reported data that suggested that for best efficacy then dose daily but for lower side effects dose intermittently.
  • Vamorolone: Dr Mercuri gave this the thumbs up based on current data with Vamorolone, a steroid alternative. He believes it shows great promise and could be a highly effective treatment with reduced side effects to glucocorticoids.
  • Tamoxifen: Dr Mercuri said this project is very promising.

Mercuri then posed a question to the audience: What role do these types of studies play in the current circumstances where we have trials taking place with very promising gene-based approaches which have the potential to restore dystrophin and therefore reduce/remove the need for ameliorative approaches.

It is still extremely important for now and the future that we address the symptoms and that we have the best possible drugs available to do this, with high efficacy and a good side effect profile.

Dr Mercuri shared concerns from clinical trial colleagues about recruitment for clinical trials aimed at treating symptoms. Patients and their families are focussed on ‘cure’ trials and this makes recruitment increasingly difficult.

Studies directly impacting the dystrophin protein.

  • Ataluren/Translarna: initial study was not great but studies since have shown clearer results, including clearly positive 6MWT. For this reason, it is important that we continue to collect data from trials for this to provide a clearer idea of the effectiveness of this treatment.
  • Exon skipping: Eugeno summarised exon skipping studies as suggesting that low percentage increases of skip-induced dystrophin are noted, but that there is nowhere near full restoration of muscle function.

Gene Therapy

Dr Mercuri highlighted the key issues with gene therapy as the following:

  • Efficacy of gene delivery
  • Persistence of gene
  • Persistence of efficacy
  • Toxicity
  • Immunology issues
  • Reduced impact in older patients?

Ezutromid- Jon Tinsley

A sad and difficult presentation came from Jon Tinsley from Summit. He presented the data from the Ezutromid trial. This trial was recently terminated when it failed show to any effect on either the primary or secondary endpoints. There were no adverse events in this trial.

Duchenne UK have heard from some parents about the disappointment children go through when their trial is terminated. We want them to know how grateful we are for the courage and determination they have shown in taking part in the trials.

We have worked with some parents in the community to create a thank you letter and certificate for anyone who has taken part in a trial that has been terminated.

Please get in touch with us if you would like your child to receive a letter and certificate from us to thank them for taking part in the trials.

Please email [email protected] with your child’s name and address and we will post these to you.

Posters at WMS

We were very pleased to have posters on several of our projects presented at WMS 2018.

Emma Heslop, the DMD Hub manager (pictured below), presented an update on the impact the DMD Hub is having on Clinical Trial capacity in the UK. 

There was also a poster presented by Professor Dirk Fischer, from UKBB, the University Children’s Hospital in Basel, Switzerland (pictured below) on the ongoing Tamoxifen trial, which is being funded by Duchenne UK. You can read the Tamoxifen poster here.


What is Duchenne Muscular Dystrophy Duchenne Muscular Dystrophy is the most common fatal genetic disease diagnosed in childhood. Children born with DMD cannot produce the protein dystrophin which is vital for muscle strength and function. Muscle weakness starts in early childhood. Many use a wheelchair by around the age of 12. As deterioration continues it leads to paralysis and early death, often in their 20s. It almost exclusively affects boys. There is no cure. In the UK there are around 2,500 boys affected and around 300, 000 worldwide. It is classified as a rare disease. 

Who are Duchenne UK? Duchenne UK is a lean, ambitious and highly focused charity with a clear vision: to fund and accelerate treatments and a cure for Duchenne muscular dystrophy. The charity has been formed by the coming together of Joining Jack and Duchenne Children's Trust, the two biggest funders of research in the UK in the last three years. Its president is HRH The Duchess of Cornwall. Its patrons include the broadcasters Krishnan Guru-Murthy and Mary Nightingale, and the sports stars Owen Farrell, Kris Radlinski and Andy Farrell. 

Duchenne UK is entirely reliant on donations to fund and accelerate the search for treatments for DMDPlease help us and donate today:
  • Direct Debit – Duchenne Direct
  • Individual Donation – Donate
  • If you are a family or friend affected by DMD you can set up your own fund with Duchenne UK – Family and Friend Funds
  • Take part in one of our fundraising events – Events
  • Text DUCH10 £10 to 70070

Published on 30 October 2018

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