Duchenne UK round up of 2017
It has been a busy year at Duchenne UK. Our mission is to look at where we can add value to the drug development pathway, and how we can help to accelerate research that will benefit the whole community. To do this we are engaging at each stage of the drug development pathway. We are funding early stage research and pre-clinical work. But we are also now funding actual clinical trials in the UK. What’s more is we are funding the infrastructure to deliver those trials; the doctors, nurses, physiotherapists and trial coordinators needed to run trials. And we are now working with companies to speed up the drug development process.
In the last 5 years (as Duchenne Children's Trust and Joining Jack) Duchenne UK has raised over £10 million. We've spent £6.5 million to date and committed a further £3.5 million to accelerating research.
Our work wouldn’t be possible without the support of the many committed and brave members of our community who fundraise for us. We’d like to thank everyone for their help, including our valued Family and Friends Fund, the members of the Patient Advisory Board, and our partner charity Alex’s Wish, and our new partners, Duchenne Now, for their constant and resolute support.
Solid Biosciences Gene Therapy Announcement
At the end of November Solid Biosciences announced the initiation of their first gene therapy clinical trial. Enrolment is underway at the first trial site in the US. Solid Biosciences is currently investigating potential trial sites in Europe.
This is a huge milestone in the work Duchenne UK has done. In 2014, Duchenne UK partnered with the Duchenne Research Fund and Joining Jack to commit $5 million to help fund pre-clinical work for Solid’s gene therapy programme. We are thrilled that, just three years later, we can share this news with our community.
For more information read our news story about the Solid Biosciences trial. We have also produced a gene therapy overview to help you better understand gene therapy, and how gene therapy could help the Duchenne community.
In November, Duchenne UK launched Project HERCULES. Duchenne UK has joined forces with industry partners who are developing treatments for DMD to launch Project HERCULES, an innovative, unique and ground-breaking multi-stakeholder collaboration. The aim is to help stakeholders better and more efficiently engage with NICE and other global bodies who decide how the government should pay for medicines.
Launch of the DMD Hub
We were delighted to launch the DMD Hub in September, to address head on the issue of expanding clinical trial capacity in the UK, so that more patients can access research and clinical trials.
Clinical research into Duchenne muscular dystrophy (DMD) research is at an unprecedented stage, in terms of the number of possible therapeutic approaches coming to trials.
Pharmaceutical companies can be reluctant to go to clinical trial sites with no previous experience of running DMD trials. This has led to bottlenecks at existing experienced sites which are reaching capacity.
The Hub’s aim, is to make more clinical sites trial ready by providing funding for posts, training, mentoring and other resources to help them achieve the requirements set by industry to run clinical trials. Emma Heslop is the DMD Hub manager, based at the John Walton Muscular Dystrophy Research Centre at Newcastle University. Emma works closely with the two DMD Hub centres of excellence: Great Ormond Street Hospital in London and The John Walton Muscular Dystrophy Research Centre in Newcastle.
We are delighted to share news that we have agreed funding for posts at Alder Hey (in collaboration with Joining Jack and Alex’s Wish) and Leeds Children's Hospital to support the clinical teams there to run more clinical trials. Exact details of the posts will be announced soon.
Duchenne UK’s mission for the DMD Hub is to ensure that all patients with DMD, both children and adults, have the opportunity to access clinical research opportunities.
Read our DMD Hub leaflet and find out more here: https://www.duchenneuk.org/dmd-hub
Newcastle Plan Achievements
We are pleased to share the update that 16 key clinical trial posts have now been funded at leading Neuromuscular Centres for Duchenne Muscular Dystrophy in the UK.
The £1.2m of funding for the posts was put together in just 6 short months, after an unprecedented meeting in Newcastle in July 2015. The meeting brought together over 70 clinical, patient organisations, industry and National Institute for Health Research representatives to address the lack of capacity at centres of excellence and other neuromuscular centres in the UK.
Since the funding received by Great Ormond Street Hospital (GOSH) and Newcastle, no more trials have been turned away:
In an update report from GOSH, Professor Francesco Muntoni said: “No studies have been turned away since this award. Actually having the staff in place has allowed us to expedite many preparatory processes of assessing new studies for adoption whereas in the preceding two years the team had turned down 10 novel experimental approaches.”
Duchenne UK is funding five posts at GOSH (research staff pictured), in collaboration with the GOSH charity, Harrison’s Fund and the Duchenne Research Fund.
The funding has been used to develop, expand and stabilise the neuromuscular research team. According to GOSH, the Lead Research Physiotherapist has been particularly valuable for Duchenne research.There’s increasing demand from patients coming to the centre, and more opportunity for people to take part in trials. More successful commercial trials are being extended beyond their completion and follow up care is being offered for longer.
Duchennne UK and Joining Jack partnered with the Duchenne Research Fund to pay for the refurbishment and upgrade of the paediatric area of the Clinical Research Facility at the New Newcastle Royal Victoria Infirmary. The area was officially opened by Professor Mark Walker and Dr Michela Guglieri on the 27th September 2017. The new space will be used by families taking part in clinical research. The opening was attended by several local Duchenne families who supported the development of the space.
Duchenne UK has been co-funding Dr Michela Guglieri’s role since 2015 – along with Alex’s Wish, Action Duchenne, Duchenne Research Fund, Harrison’s Fund and Joining Jack. She is integral to the Newcastle team both in developing and delivering clinical trials. She has also been integral to creating the DMD Hub and supervises two clinical research associates and a clinical research nurse in Newcastle.
Unveiling of the newly refurbished paediatric area in the Clinical Research Facility at Newcastle Royal Victoria Infirmary:
Tamoxifen Trial will start in first half of 2018
Duchenne UK is collaborating with two European patient organisations, and a European E- rare grant, to fund a study to investigate the safety and efficacy of Tamoxifen as a treatment for DMD. The trial had been due to start this year. Unfortunately there have been some delays and the trial will now start in 2018. The first and second trial sites in the UK for the study will be Alder Hey children’s hospital in Liverpool and Leeds Children's Hospital.
Tamoxifen has been used to treat breast cancer since the 1980s. It is also used for hormonal disorders in pre-pubescent boys. Preliminary data in the DMD mouse model (Dorchies et al. 2013) demonstrated that Tamoxifen reduced fibrosis, increased the thickness of muscle fibres, and resulted in a delay in disease progression.
Investigating Simvastatin as a potential disease modifying therapy
In collaboration with Solid Biosciences and Dr Stan Froehner and Dr Nick Whitehead, University of Washington, Duchenne UK is investigating whether the use of statins may provide skeletal and cardiac muscle functional benefits.
In DMD, muscle cells come under significant stress, which leads to cell death, chronic inflammation and fibrosis. Statins are a class of molecules approved in many countries for their known benefits in heart disease. Recent findings have shown that statins may also have anti-oxidative and anti-inflammatory effects. In preclinical models of DMD, short-term administration of Simvastatin resulted in reduced skeletal and cardiac muscle damage and enhanced muscle function. Long-term administration in the same models showed an improvement of overall muscle health and function.
The research group has completed the majority of an in vivo efficacy study to compare the potential class effects of statins to previously published beneficial data of simvastatin in mdx mouse models of DMD. This study is being completed in a blinded manner, comparing multiple statins with varying profiles. The outcomes being measured are potential effects on muscle function and histopathology as indicators of treatment benefit. In addition to efficacy readouts, mass spectrometry will be performed to correlate muscle distribution of statins to observed effects.
Results generated through these preclinical analyses will inform the decision to pursue Simvastatin as a potential clinical therapeutic candidate for DMD. Data is expected to be available at the end of 2017.
PepGen Update: Peptide platform technology for enhanced oligonucleotide delivery
This project aims to further develop peptide-oligonucleotide conjugate drugs to provide a more effective therapy for Duchenne muscular dystrophy (and related conditions including spinal muscular atrophy) by improving the delivery of exon-skipping drugs.
The update report stated that work is progressing well against the various agreed aims and milestones. They have generated extensive in vitro and in vivo efficacy data for the project.
These novel peptide classes show high efficacy following a single intravenous administration and outperform the industry standards. Data is being finalised to prepare to file a patent with the aim of forming a robust IP foundation supporting next generation peptide technologies.
They have produced efficacy data in disease models and have been working intensively towards generating safety and therapeutic index data, developing business plans and getting advice on clinical development plans. They are in the process of establishing a PepGen as a spinout biotech company.
Elastase inhibitors Update: Use of neutrophil elastase inhibitors to treat DMD
The initial report into the use of the trial into neutrophil elastase inhibitors shows good progress. The trial explores how to use inhibitors to counteract muscle damage and promote muscle regeneration by manipulating the body’s response to inflammation.
Researchers have successfully completed the in vitro and on-cell experiments exploring 8 concentrations of inhibitors, and selecting the most appropriate. The effects of the inhibitors were compared in mouse and human elastase to see which inhibitors best translate between the two groups. Tests have been carried out to ascertain the most effective daily drug intake in food.
New faces at Duchenne UK
David Bull has joined us as Director of Research. David spent 16 years as a research scientist at what became GlaxoSmithKline. Initially trained as a neuroscientist studying novel treatments for Parkinson’s Disease and Schizophrenia, David then led the research team looking into the molecular biology of 5-HT receptors in terms of treating migraine.
David then moved into science development in the UK and USA and led the UK Learning & Development team, subsequently becoming VP Leadership & Organisation Development for GSK International. David has worked as an independent consultant for the last few years.
Naomi Litchfield has taken on the role of Director of Patient Engagement and Clinical Care following feedback from the Duchenne community that this area needed full time support and focus.
Patient Information Day
In July 2017 we invited patients and caregivers to a free information day at Alder Hey Children's Hospital, to share with them some of the trials we've funded, update them on the work we are doing, and to give advice and information about how to access research and clinical trials of potential treatments for Duchenne Muscular Dystrophy.
Duchenne UK is hosting its second free Patient Information Day on Friday 23rd February 2018, at UCL Great Ormond Street Institute of Child Health in London.
To register visit: https://duchenneuk.eventbrite.com.
We are also running a free Patient Information Day in Glasgow on Saturday 12th May 2018. We will launch this in the new year.
Patient and Caregiver perspectives on Duchenne Clinical Trials Survey Report
In the summer of 2017, Duchenne UK launched its first patient survey, to better understand patient views on accessing clinical trials and research. The survey was entitled, “A questionnaire to understand Duchenne patient and caregiver perspectives on Duchenne clinical trials”.
The survey is part of our community engagement work to better understand what patients and caregivers want from care, research and clinical trials.
The sessions were focused on what clinical trials are coming up in the UK in the next 12 months, and how patients can access them. There were also updates on care and supporting the learning and education of children and adults living with Duchenne Muscular dystrophy.
The aim is to help the Duchenne community to better understand the current clinical trial recruitment process, and to see where we can make improvements to create a fair and equitable trial recruitment process. The survey also aligns with Duchenne UK’s broader mission and the DMD Hub to ensure that all patients with Duchene have access to clinical trial opportunities.
You can read the survey report at:
Or watch the report being presented in a video here:
Duchenne UK is proud to be supporting Decipha, an educational support programme to provide advice and guidance to families educational needs and Education Health and Care Plans for Young People.This invaluable resources is available FREE to families, thanks to Duchenne UK’s support.
Decipha is run by Nick Catlin. He and his team have been working hard on Decipha's RoadMap for Life project. Two recent reports from OfSTED and the Social Care and Local Government Ombudsman highlighted the failures by local authorities to deliver Education Health and Care Plans (EHC Plans) for young people with Special Educational Needs and Disabilities (SEND), Decipha aims to address these issues and assist families with these plans for Education, Health, Social Service and Care provisions
Decipha has had an increasing number of requests for assistance from Duchenne families who are struggling to get started on the planning process and access the correct assessments to identify SEND of young people and adults living with Duchenne Muscular Dystrophy.
Decipha strongly recommend that all young people and adults in education or training from 0-25 years with Duchenne apply for an EHC Plan or the equivalent outside of England.
Nick Catlin from Decipha said:
"A joined up Roadmap for Life is crucial for every young person and family to ensure that they have every opportunity to fulfil their aspirations and for the young person or adult to gain the skills and qualifications they need for the future. We can offer advice and support and guide families through the EHC Plan process that is backed by government legislation in England.
DMD Pathfinder's and Muscle Owl
Naomi from Duchenne UK and Jon Hastie from DMD Pathfinders appeared on Muscle Owl to discuss the Adult preferences and opportunities in research. We will be launching an advisory group and a number of surveys soon for adults to take part in.
You can watch the Muscle Owl episode here: https://youtu.be/jonekxS6hns
Duchenne UK submits evidence at the House of Lords Science and Technology Committee inquiry into the impact of Brexit on UK Duchenne muscular dystrophy research
Duchenne UK outlined the benefits of continued collaboration with European agencies post Brexit. The charity submitted evidence about how European programmes have contributed more than 22-million euros to DMD research in five years. It raised concerns about the recruitment of specialised medical staff needed for clinical trials many of which are from outside the UK. It also said Brexit might stifle the UK’s contribution to the international scientific and medical communities and said the loss of involvement of the EU’s regulatory pharmaceutical framework could make the UK a less attractive place for firms to launch new drugs and conduct clinical trials which could impact on the ability of patients to access lifesaving drugs.
You can read Duchenne UK: Written evidence to the House of Lords Life Sciences and the Industrial Strategy inquiry here: https://bit.ly/DUKHOL
THANK YOU FOR YOUR SUPPORT
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: