Research we are funding

From the very early days of Action Duchenne, we have supported research into gene therapy as a potential way of treating Duchenne muscular dystrophy. This area has seen significant progress in recent years, and now is the time to test its safety in people living with Duchenne, here in the UK.

This international collaboration will assess the safety of gene therapy in Duchenne, in a phase I/II clinical trial that will take place in both the UK and France. As these will be the first gene therapy trials for Duchenne in the UK, UNITE-DMD will be vital to test the safety of this technology.

Together with the principal funder Muscular Dystrophy UK, we are investing over £1.6m into UNITE-DMD. The French Muscular Dystrophy Association (AFM-Téléthon) is funding the French arm of the project.

Click here for full article about UNITE-DMD

The Chief Scientist Office in Scotland, Action Duchenne and Muscular Dystrophy UK are working in partnership to make possible the award of a clinical academic training fellowship to Dr Shuko Joseph at the University of Glasgow.

Dr Joseph has been awarded the funds for a three-year project, ScOT-DMD to better understand bone deterioration in the 2,500 children and young people living with Duchenne muscular dystrophy in the UK. The £239,000 project is funded equally by the three organisations.

Dr Joseph will use state-of-the-art imaging technologies and biological ‘markers’ to study bone health in people with the condition, and will work with healthcare professionals across Scotland to ensure the best possible protective care.

Alongside laying the foundations for treatments to reduce breaks, Dr Joseph’s appointment will also increase the country’s capacity for clinical trials. With no treatment addressing the underlying cause of Duchenne muscular dystrophy currently widely available in the UK, greater  clinical trial capacity is vital to allow children to benefit from potential therapies, and for new treatments to be developed for Duchenne.

Here at the National Hospital for Neurology and Neurosurgery in London, we are delighted to learn that Action Duchenne has awarded us a grant to be used as a ‘bridging fund’ for the setting up of new clinical trials for adults with Duchenne muscular dystrophy. We have a growing number of adult Duchenne patients attending our multi-disciplinary service, currently in the region of 100 men affected with the condition. Our goal is to provide the best care that we can and to do our upmost to ensure that adults with Duchenne are given the opportunity to participate in clinical trials.

Currently, there are in the region of 21 pipeline drugs in development for Duchenne. To date almost all of the clinical trials have been undertaken in children and use walking measures, such as the 6 minute walk test, as the primary outcome measure. Very recently, we were really excited to be given the opportunity to participate in a ground-breaking trial, but faced the difficulty of not having sufficient resources in place to set up the trial or run it in the initial stages. This is because funding for industry sponsored trials is reimbursed in small amounts each time a patient visits for the trial. As a consequence, it will take at least 12 months before sufficient funds are reimbursed by the company to employ researchers to perform the trial measurements. Thankfully, our staff are so committed that they have been running this study, so far, on a voluntary basis in their own free time. This is clearly not sustainable in the long-term, since they could choose to stop doing this at any time.

Having insufficient staff to setting up and run clinical trials in the early stages is likely to be a problem that arises again in the future. Because of this, we approached Action Duchenne for a small ‘bridging trial set-up fund’ to enable us to fund researchers for a small amount of time so that the trial can continue to run and so that we have the resource to set up similar trials for adults with Duchenne  in the future.

Thank you Action Duchenne!

A novel device called ActiMyo® has been proposed for its use as an outcome measure in ambulant and non-ambulant Duchenne trials. ActiMyo offers the opportunity to conceptualise shorter studies with much less patients compared with the currently available outcome measures. It is a portable device capable of providing information registered through an accelerometer, a magnetometer and gyroscope. A further validation of ActiMyo in a large sample including both patients and healthy volunteers will provide essential information of how this tool would work if used as primary outcome in pivotal studies.

The purpose of this project is to generate normalized standard scales for control subjects based on the data gathered from 80 healthy children (6-17 years old).

Following 12 months of enrolment, subjects will carry the device during 4 weeks twice within a 12 months interval. A total of 12 ActiMyo® devices will be allocated to this study, which will allow enrolling the expected number of subjects over a 12 months period.

The project will be conducted in Liège neuromuscular center, in Belgium. Belgian regulation allows recruitment of healthy subjects in school. The recruitment strategy is to propose two schools take part in the project as part of their pedagogic project. We will propose at first a lecture and debate in each class about research and Duchenne muscular dystrophy, and ask the children and parents to take part in the study. This study will, of course, be validated by the Ethics committee. We believe that this approach will be highly efficient for recruiting participants from different age groups, and in addition help to generate conscience about the importance and the need of research in Duchenne.

Dr Laurent Servais, Chief Investigator in this project and Key Opinion Leader in Duchenne said: “In this context, identifying robust, objective, precise, reliable and reproducible follow-up tools, that objectively measure patient´s motor capacity, and thus serve to analyse and compare the response to emerging treatments, is needed. Then, the clinical development plan in DMD will be shorted, cheaper, and the risk of false-negative trials will decrease.  The whole Actimyo team is very excited to work with the support of action Duchenne on this project.”

The Director of Research at Action Duchenne added, “We are delighted to fund this pivotal work in validating a potential outcome measure for Duchenne trials, which may be applicable to all ages of the Duchenne spectrum. This is in sum reflects the ethos of Action Duchenne in meeting the needs of the whole community and also collaborating internationally to drive translational Duchenne research and clinical trials forward.”

Action Duchenne, Alex’s Wish, Duchenne Now and Harrison’s Fund are  co-funding a research project.  Called Repurposed Cancer Therapeutics as Treatments for DMD, the project will be led by Professor Steve Winder in the Department of Biomedical Science at the University of Sheffield.

With a total cost of £120, 935, this project hits the strategic aims of each of the funding charities by showing the potential to treat all Duchenne patients and the possibility of a fast track to the clinic.

The project will investigate the use of four drugs that are currently used to treat cancer as potential treatments for Duchenne, using mouse models. The project aims to assess:

1.    the long-term efficacy of three tyrosine kinase inhibitors in reducing the dystrophic patho-physiology in mdx mice.

2.    the long-term efficacy of a proteasome inhibitor in reducing the dystrophic patho-physiology in mdx mice.

3.    the possible synergistic effect of tyrosine inhibitors combined with proteasome inhibitors in further reducing the dystrophic patho-physiology in mdx mice.

In people living with Duchenne Muscular Dystrophy, a faulty signal in the cell acts as a switch which leads to disruption of the muscle cell surface.  This ‘faulty switch’ is part of the cause of Duchenne.  If this ‘faulty switch’ could be turned off it could stop or reduce the muscle damage associated with DMD. Some cancers are caused by the same kind of faulty switch, and therefore the same drugs that are used to treat these cancers may also have therapeutic benefit in Duchenne.

The team behind this project have previously experimented with these drugs in zebrafish models that have Duchenne, where they worked as expected.  They have also used two of the compounds on mdx mice, with encouraging results.  The next step is to use all four compounds individually and in combination in mouse models, over a longer period of time.  If successful this project will be a crucial step in gaining approval for a clinical trial of these treatments in human subjects.  Because the drugs used in this project are already approved for cancer patients they could potentially be fast tracked to the clinic for Duchenne patients if this research project is successful.

Barts Charity and Action Duchenne have combined forces to support research into new stem cell therapies for Duchenne Muscular Dystrophy. With a combined award of £276,000 (£250,000 from Barts Charity and £26,000 from Action Duchenne) they will be supporting the research of Dr Yung-Yao Lin, lecturer at the Barts and The London School of Medicine and Dentistry, Queen Mary University of London.

We are delighted to co-fund this project with the Barts Charity. This was an integral part of Action Duchenne’s updated research strategy released last year, supporting promising new techniques that will lead to further advances for Duchenne and Becker Muscular Dystrophy.

Dr Lin’s lab has developed novel gene-corrected muscle stem cells, generated from the patient’s own skin, that offer a potential therapeutic agent for Duchenne Muscular Dystrophy (DMD). This award will fund a feasibility study to produce the data needed to start clinical research. Muscle stem cells (myogenic progenitors) can regenerate muscle fibres and replenish the muscle. The project will explore whether transplanting DMD gene-corrected muscle stem cells generated from patients’ own skin cells, will reduce the risk of immunological rejection and the need for life-long immunosuppression, bringing new hope for people affected by this devastating disease.

Muscular dystrophies are debilitating genetic diseases characterised by progressive weakness and wasting of skeletal muscle, which is responsible for voluntary movements and breathing. Gene mutations lead to loss of muscle fibres and their replacement with fat and connective tissue. Current standards of care can delay loss of ambulation, cardiac and respiratory problems, but patients develop progressive weakness leading to immobility. Some muscular dystrophies cause premature death.

“We are delighted to co-fund this project with the Barts Charity. This was an integral part of Action Duchenne’s updated research strategy released last year, supporting promising new techniques that will lead to further advances for Duchenne and Becker Muscular Dystrophy”

Dr Yung-Yao Lin, Queen Mary University added: “We are grateful to receive the joint award from Action Duchenne and Barts Charity. This award will allow us to further advance the development of cell therapy for treating muscular dystrophies. Our study will pave the way for a first-in-human safety clinical trial. Our collaborative team is very excited to work with both charities on this innovative project.”