DMD research

17th International Conference on Duchenne and Becker Muscular Dystrophy

20th February 2019

Last weekend, Alex Johnson, Dr David Bull and Megan Mullany represented Duchenne UK at Duchenne Parent Project Onlus’s 17th International Conference on Duchenne and Becker muscular dystrophy in Rome.

The annual event brings together industry, academics, patient organisations and families from Europe and beyond, to discuss the current research in Duchenne and Becker muscular dystrophy.

The first session, titled Restoring dystrophin (part 1), focussed on therapies treating DMD by restoring the expression of dystrophin. Pfizer, Solid Biosciences and Sarepta Therapeutics updated the community on their microdystrophin gene therapy clinical trials. You can read more about gene therapy and the progress of these trials here. Ronald Cohn (SickKids, Canada) then discussed genome editing using CRISPR/Cas9 technology. CRISPR has the potential to treat DMD by editing the genome to correct the mutation this could be efficacious for different types of mutation such as deletions, duplications. CRISPR technology is still in early pre-clinical stages but it could provide a powerful gene editing tool once safety and delivery effects are addressed.

With the physical effects of DMD come mental and cognitive difficulties. The second session of the meeting, ‘When complexity increases: DMD/BMD and related issues’, brought together therapists and psychiatrists to discuss the importance of assessing the treating these complications. A third of patients with DMD have cognitive difficulties, including speech impediments and learning difficulties. Children with a mutation after exon 44 have a higher chance of developing these problems. Although this area is not well understood, this could be because the mutation prevents the formation of dystrophin isoforms which should form in the brain. Marika Pane, a children’s neuro-psychiatrist, highlighted that most children with DMD have motor delay and delayed speech and suggested this could be used as an indicator in young children to diagnose DMD early. The other speakers in this session spoke about the need for multidisciplinary treatment for DMD, the neuromuscular doctors, physiotherapists should work alongside occupational therapists and psychologists that have been trained in DMD. It is important for families to work with their child’s therapist to identify an approach that works for their child, at home and school, and for their family. Giancarlo Onger, a support teacher for a child with DMD, reminded us that before anything else, we should see the child as a person and not see their disabilities.

Earlier we heard about therapies treating the cause of DMD, by restoring dystrophin expression. The next session, ‘Improving muscles’, was about treating the effects of DMD. The first update was from Italfarmaco about their Givinostat clinical trial. Givinostat is thought to have anti-inflammatory, anti-fibrotic and pro-regenerative effects on the muscles. The placebo controlled phase III trial, which is still recruiting in the UK, has begun. This trial is designed to gather the data needed to get market authorisation for the use of Givinostat for DMD. We then heard from Roche about RG6206, a myostatin inhibitor. After a successful phase Ib/II study, the phase II/III pivotal trial, will gather data on the efficacy of the treatment. In August 2018, Pfizer terminated the development of Domagrozumab, a different myostatin inhibitor, after the drug did not meet primary efficacy endpoint in a phase 2 clinical trial. The trial was not terminated due to safety. A representative from Pfizer addressed the results of this study and the post-hoc analysis they have done since. The data gathered from this trial is of high quality and Pfizer hope to use it to help develop new therapies for DMD. The final presentation from this session was about the long-term effects of Idebenone (Raxone) on respiratory function, from Santhera. Santhera have collected promising real world data from 18 patients for up to 6 years after the DELOS phase III study. The SIDEROS trial, another phase III study for Idebenone, is ongoing and is recruiting in the UK.

Day two of the conference started with a session titled Restoring dystrophin (part 2), focussing on therapies that restore dystrophin expression using exon skipping and stop-codon read through. Sarepta presented the 11 exon skipping programmes they have in the pipeline for DMD. The ESSENCE trial, a phase III study for two of Sarepta PMO programmes (exon 45 and 53 skipping therapies) is ongoing and recruiting at some sites in the UK. Sarepta are also developing PPMO’s, which adds a cell penetrating protein to improve uptake of the drug. In animal models, PPMO’s have been shown to increase dystrophin expression compared to PMO therapies. Wave Life Sciences also have exon skipping therapies in the clinic. A phase I study for exon 51 skipping is ongoing, including sites in the UK. Wave use platform technology to generate stereopure oligonucleotides, they believe this improves the efficacy of the treatment compared to standard oligonucleotide production methods. The final presentation in this session was from Eugenio Mercuri, about PTC Therapeutics’ Translarna (Ataluren). Translarna is a stop codon read-through drug, which can be used to treat a small subgroup of patients with DMD, who have a non-sense mutation in the dystrophin gene. This treatment is licensed for use in the EU and an ongoing post marketing observational study of Translarna is still recruiting in the UK, to collect real world data about the effect of the drug.

The final clinical update of the conference was titled ‘Improving muscles & opposing inflammation processes’. The first presentation came from ReveraGen BioPharma about Vamorolone. Vamorolone is a steroid alternative which aims to maintain the efficacy of steroids but eliminate the side effects. VISION-DMD, the phase IIb trial for vamorolone is ongoing and has begun recruitment at sites in the UK. Next, was Catabasis with Edasalonexent, an NF-kB inhibitor which could also provide an alternative to steroids. The phase III POLARIS DMD trial is ongoing and it is anticipated sites in the UK will open in the coming weeks. Edasalonexent could preserve muscle function and slow DMD disease progression. The final steroid alternative to be presented was MNK-1411 by Mallinckrodt Pharmaceuticals. The phase II BRAVE study is not currently ongoing in the UK. Last, but my no means least, to the stand was Dirk Fischer, presenting the TAMDMD trial. This phase III clinical trial is studying the use of Tamoxifen for both ambulant and non-ambulant patients with DMD. Tamoxifen has been used to treat breast cancer since the 1980s and is also used for hormonal disorders in pre-pubescent boys. 

DMD Hub Poster & DUK

Preliminary data in the DMD mouse model demonstrated that Tamoxifen reduced fibrosis, increased the thickness of muscle fibres, and resulted in a delay in disease progression. The trial is ongoing in Switzerland and Germany and hope to open at other sites in the coming weeks.

In addition to the clinical research presentations, the conference provided a great opportunity for Duchenne UK to meet one on one with academics and companies in the DMD field. In the poster sessions, researchers and organisations showcase the findings and progress of their work. Cathy Turner presented a poster on the DMD Hub. Cathy is the DMD Programme & TACT Coordinator, based at The John Walton Muscular Dystrophy Research Centre at Newcastle University, her post is funded by Duchenne UK. 


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 treatment or 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. 

How to donate?
Duchenne UK is entirely reliant on donations to fund research for treatments and a cure to DMD. This can be done via:

For more information and interview requests:
Visit www.duchenneuk.org
Molly Hunt – Communications Manager, Duchenne UK 
E: [email protected]

Published on 20 February 2019

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