10th April 2019

Last week, our co-founders and research team attended The MRCs 12^th UK Translational Research Conference for Neuromuscular Diseases, which was held at the Centre for Life in Newcastle.

Day One of the conference began with the launch of the MRCs International Centre for Genomic Research in Neuromuscular Diseases. The initiative is a partnership between UCL, Newcastle and Cambridge universities with international centres in South Africa, Brazil, Zambia, Turkey and India to research neuromuscular diseases globally.

The afternoon was dedicated to the major contributions of Kate Bushby, a clinical academic, who was based at the John Walton Muscular Dystrophy Research Centre and recently retired. Throughout her career, she has driven the neuromuscular disease field greatly forwards, both in terms of research and care. The presentations in this session covered the DMD standards of care, the North Star network, FOR-DMD – an ongoing study designed to determine the best glucocorticoid steroid regimen for DMD, VISION-DMD – the phase 2b study for glucocorticoid alternative Vamorolone, EURO-NMD and the DMD Hub.

We were very pleased to have our DMD Hub manager, Emma Heslop, presenting the work of the DMD Hub at the conference. Her presentation explained how the DMD Hub is increasing clinical trial capacity in the UK, by providing funding and advice to sites that want to take on more clinical trials but are limited by their resources. As well as funding, the DMD Hub provides information and advice to patients, industry and clinical trial sites to increase knowledge and expertise about trials and research. On the DMD Hub website, the clinical trial finder is a popular tool particularly with patients and caregivers looking for clinical trials in the UK.  During Emma’s presentation, she explained the newly launched DMD Hub Toolkit - which holds a variety of resources for industry and trial sites to help set up trials, and to promote a common approach to conducting research in the UK. Emma also presented a poster about the work of the DMD Hub at the conference.

The second day started with several presentations focusing on DMD research. Charles Gersbach spoke about using CRISPR/Cas9 Gene Editing to treat DMD. CRISPR could allow us to edit a patients own DMD gene, correcting the mutation and allowing them to produce full length or nearly full length dystrophin. Early mouse work delivering a CRISPR Cas9 DMD therapy to mdx mouse using an AAV vector has been promising, but Prof Gersbach highlighted there is a long way to go with this research and it is still very early stage. There are hurdles we need to overcome, including the off-target cutting of the CRISPR/Cas9 complex as well as AAV integration into the genome.

Kevin Flanigan, from Nationwide Children’s Hospital, presented some alternative gene therapy approaches. The first he discussed was the surrogate gene therapy - an approach which is currently being pursued by Sarepta Therapeutics through their GALGT2 programme. This approach uses AAV to deliver the GALGT2 gene, which produces a protein involved in the utrophin complex. This, in turn, promotes an over-expression of utrophin, which acts as a surrogate for dystrophin and stabilises the muscle membrane. The second approach he presented was using AAV to deliver an exon skipping therapy. It was recently announced that Audentes Therapeutics is developing a gene therapy approach for DMD to induce exon 2 skipping for DMD with duplications in exon 2 and mutations in exons 1-5 on the DMD gene.

Other presentations included Barry Bryne, University of Florida, highlighting the immunology issues we must consider in Gene Therapy for Neuromuscular diseases. This is important both for tackling pre-existing antibodies and the re-administration of AAV gene therapy.

In addition to the presentations about clinical and research updates, there were several poster sessions, which gave us an opportunity to speak to researchers Duchenne UK have funded in the past, as well as discuss new potential projects.

One excellent poster presented some preliminary results from an ‘observational’ study looking at the potential for testosterone to be used as a treatment approach, to reduce the impact of corticosteroids in causing pubertal delay in DMD boys. This study comes from Volker Straub’s lab in Newcastle and was led by Dr Claire Wood and funded by Duchenne Now. Last month Duchenne UK announced a £228,562.51 grant to extend this project to see whether testosterone treatment to induce puberty is enough to support long term testosterone production.

NOTES FOR EDITORS

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:

• 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 DUCHENNE to 70085 to donate £5. This costs £5 plus a std rate msg.

For more information and interview requests:

Visit www.duchenneuk.org

Molly Hunt – Communications Manager, Duchenne UK 

E: [email protected]