Tuesday 17th December 

TREAT-NMD Summary

Last week, Dr David Bull, our Director of Research, attended Treat-NMD’s conference in Leiden. This is an important meeting to ensure we are up to date with all patient advocacy and DMD research, as well as meeting up with many of our international partners including researchers, pharmaceutical companies and our friends at other patient organisations around the world.

Here is a summary of many of the sessions David attended:

Welcome address

Professor Annemieke Aartsma-Rus, who sits on our SAB, gave the welcome address. During the conference, we were delighted to hear the announcement that Annemieke was honoured with the EURORDIS Black Pearl Scientific Award which “recognises Professor Aartsma-Rus’ exceptional achievements and dedication in the field of Duchenne Muscular Dystrophy”. Annemieke’s team at Leiden were also one the recipients of our DMD Major Grant Call this year, read more about that here.

Future of patient advocacy panel session

There was an emphasis on improved and more intimate association between patients and the companies. At Duchenne UK, we work closely with many companies to make sure the patient is always at the heart of drug development.

Sarepta/Biogen Symposia

Sarepta and Biogen held a symposium on “Evolution of Patient Registries and current status”. They highlighted the increased need for collecting DMD data and making better use of this data for feasibility/recruitment to trials, post market surveillance and data for regulators. They aim to develop a scalable registry that can address needs of different stakeholders including industry/clinicians/patients.

Exercise in NMD: Dr Nicole Voert

Dr Voert presented a study of physical inactivity in FSHD (Facioscapulohumeral muscular dystrophy). A trial of 225 patients showed physical activity had a positive benefit on fatigue, increase of general physical activity and 70% of patients say they are still doing their exercises after 5 years. The MRI scan in FSHD seemed to reduce the increase of fat infiltration into leg muscles. This study was in FSHD, but there is a real belief that exercise is good in all Neuromuscular disease areas.

Historically, DMD patients were kept ‘immobile’ due to fear of activity-induced muscle damage. However now we know that activity of a low level is not damaging – indeed it’s good for them and must be continued – it will revert if you stop!

At the end of this session, there was a discussion on whether there was such a thing as too much exercise for DMD patients. Contributors to the discussion suggested that yes it can be harmful and depends on the condition and the individual. Exercise should be prescribed like a medicine and be personalised. One speaker said that it was different for DMD – be very careful never to exceed 70% of maximum force possible. DMD is a different cause of muscle damage and exercise is still good, but more care needs to be taken. If the exercise stops you performing your normal daily life then you’re doing too much. Same if you get pain for more than 24 hours.

Personalised medicines – Dr Jinkuk Kim

Dr Kim from, Boston Children’s Hospital, shared an interesting study looking at how it could be possible to go from developing understanding of genetics in an individual to creation of a specific oligo treatment in 8 months. The focus was on a girl called on Mila who had CLN7 Batten disease – a truly devastating, fatal disease with no current therapy.

There seemed to be a rationale for using a specific-to-Mila antisense oligonucleotide (ASO) but time for development was against them. They decided to go to the FDA and ask to be allowed to apply the data from Nusinersen, as a principle, to anything they could create for Mila. They were successful and developed an ASO for Mila’s mutation which the FDA supported. Mila is now stabilised and doing well. The lesson here could be applied to the work we do via Project HERCULES – working with regulatory agencies to share non-proprietary data to speed up processes. Similarly, we are asking the EMA to allow us to use placebo data from tamoxifen trials to be applied to other similar trials – again saving time and reducing the number of boys allocated to a placebo arm. PPMD are trying a similar approach with their Platform trial work.

Next steps in CRISPR/Cas9 – challenges and possibilities: Charlie Gersbach

This session was about editing at the DNA nuclear level – essentially using gene cutting and stitching to remove mutated DNA from the cell nucleus.

To do this they use CRISPR as the guide - identifying specifically where to make a cut in the DNA, and then the enzyme Cas9 to do the cutting out and rejoining.

Several studies have replicated this work and so, despite differences in doses, exons, manufacture etc – they all seem to work, suggesting this approach could be a valid one These are still many issues to overcome – immune responses, durability of the cut and only microdystrophin as the result (so far) but these will be overcome with time, money and research. We should be watching and supporting anything in this area.

Someone asked the question as to whether patients should wait for CRISPR study  rather than accept a current gene therapy trial – the view from Gersbach (and others in the audience) was that people should not wait for CRISPR – DMD is degenerative so take the best that is available at the moment. It’s still a personal choice, though.

Patient reported outcome measures in neuromuscular diseases: Stojan Peric

What we actually measure in outcome measures is impairment, ability and quality of life. The presentation discussed many of the elements needed for a clear and precise tool. It was interesting to note that Chad Heatwhole was quoted in the presentation and he is the lead investigator in a project DUK and PPMD are jointly supporting into the creation of a validated PRO to be used in future clinical trials. You can read more about our PRO project here.

Project HERCULES Poster:

Duchenne UK also had a poster at the meeting about Project HERCULES. Fleur Chandler was there to present the poster. Fleur chairs the Project HERCULES Steering Group and also sits on the Patient Advisory Board of Duchenne UK.

If you have any questions, please email [email protected]

NOTES FOR EDITORS

What is Duchenne Muscular Dystrophy?

Duchenne muscular dystrophy (DMD) 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.

We are investing millions of pounds in research right now to bring treatments and a cure to help this generation. Duchenne UK is the largest funder of DMD research in the UK. We are also committed to accelerating the pace of research. 90p in every £1 raised is committed to research.

Our president is HRH The Duchess of Cornwall. Our patrons include the broadcasters Krishnan Guru-Murthy and Mary Nightingale, and the sports stars Owen Farrell, Kris Radlinski and Andy Farrell. 

We need your help, because we need to keep funding promising new research.

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 visit www.duchenneuk.org