Paving the way to treatments - our research strategy 2013- 2018

Muscular Dystrophy Campaign

Paving the way to treatments Our research strategy 2013 – 2018

About us The Muscular Dystrophy Campaign is the leading UK charity fighting muscle-wasting conditions. We are dedicated to beating muscular dystrophy and related neuromuscular conditions by finding treatments and cures and improving the lives of everyone affected by them.

Our work has five main focus areas: 1 we fund world-class research to find effective treatments and cures 2 we provide practical information, advice and emotional support for individuals with muscle-wasting conditions, their families and carers 3 we campaign to bring about change and raise awareness of muscular dystrophy and related neuromuscular conditions 4 we award grants towards the cost of specialist equipment, such as powered wheelchairs 5 we provide specialist education and development for health professionals.

Leading research. Supporting people.

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Paving the way to treatments

Welcome The Muscular Dystrophy Campaign remains at the forefront of neuromuscular research in the UK and we have made a massive investment in pioneering research since the charity was formed in 1959.

With support from our members and funders, we have helped build the infrastructure, train the scientists and support the most promising new research avenues.

The pages that follow outline the ways in which we intend to build on these vital foundations. Muscular dystrophy and related neuromuscular conditions affect around 70,000 people in the UK, and no effective treatment or cure is currently available for the majority of these conditions. Their development remains the ultimate goal at the very heart of the research the Muscular Dystrophy Campaign funds.

Research is at the very heart of the charity, and our investment would not be possible without our supporters. So we would like to take this opportunity to thank you for that support.

Robert Meadowcroft Chief Executive

Dr Marita Pohlschmidt Director of Research

Our research strategy 2013 – 2018

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Executive summary The Muscular Dystrophy Campaign is the leading UK charity providing support for more than 60 different muscular dystrophies and related neuromuscular conditions affecting 70,000 people.

The charity was founded in 1959 as a medical research charity and funds internationally competitive research with a strong UK focus.

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ince our foundation, our investment in science has led to the identification of many genetic defects that can cause a neuromuscular condition. This in turn has led to improved diagnosis and care and has given scientists a better understanding of muscle function and the underlying biological processes leading to muscular dystrophy or one of the related neuromuscular conditions.

Research funded by our charity has spearheaded some groundbreaking therapeutic developments that are now being tested in clinical trials. This has also been the catalyst leading to further major funding from institutions such as the MRC and the Wellcome Trust, an example of which is the establishment of the Wellcome Trust Centre for Mitochondrial Disease at Newcastle University.

The research strategy describes eight different strategic goals in which investment is required.

These are:

GOAL 1 To develop potential therapeutic approaches

GOAL 2 To promote clinical trial readiness

GOAL 3

The muscular dystrophies and related neuromuscular conditions are regarded as rare or, in some cases, ultra-rare with as few as 10 known individuals affected by them in the UK. This is the reason why they are often overlooked by government and other funding agencies, the academic community and the pharmaceutical industry. In recent years this has been starting to change with the establishment of international initiatives and networks that aim to bring together globally available resources and to implement the infrastructure necessary for promoting clinical trial-readiness.

To support clinical trials and pilot studies

In light of these developments, and as a requirement of our AMRC membership, as a charity we have re-assessed the aims we set out in our research strategy defined in 2007. The challenges are numerous. We fund research into many conditions, all of which are at different stages in the search to finding treatments. Identifying the research areas that promise to make the greatest scientific advancements and also have the most relevance for our families is crucial to maximise the impact of the limited funds that are available.

GOAL 5

Because the conditions are rare, it is also fundamental for us to align our activities with international developments to make sure we do not fund research in the UK that duplicates research ongoing elsewhere in the world. We also want to ensure the UK is well prepared to participate in international clinical trials so that our families have early access to what could be potentially life-saving treatments.

To improve quality of life

In the pages that follow, we outline our eight strategic topics in which investment will be essential to build on the successes of the last decade and to finally bring to the market those treatments that are so desperately needed. To demonstrate the impact of our research programme, we have included summaries for a small selection of the approximately 60 conditions the charity supports.

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Paving the way to treatments

GOAL 4 To understand the cause of neuromuscular conditions

To build clinical and scientific capacity

GOAL 6 GOAL 7 To foster sharing of knowledge and networking

GOAL 8 To build partnerships

Our research strategy 2013 – 2018

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STRATEGIC GOAL 1

To develop potential therapeutic approaches In recent years the development of therapeutic approaches has made great advances and a number of promising technologies are already being tested in clinical trials for conditions such as Duchenne muscular dystrophy and spinal muscular atrophy (SMA).

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here are a number of conditions for which the underlying biological processes are well understood but no effective treatment is available. For those conditions, the development of potential therapeutic approaches is either at the pre-clinical stage – which means they are being developed in the laboratory – and/or at the clinical trial stage.

There are several different therapeutic approaches however that have great potential to develop into an effective treatment.

Exon skipping is a technology first developed in the early 1990s for Duchenne muscular dystrophy. It is aimed at masking the genetic defect in the dystrophin gene and leads to the production of a shorter but semi-functional dystrophin protein. It is not a cure but the hope is that the severe symptoms of boys and young men with Duchenne muscular dystrophy can be changed into milder ones similar to those seen in Becker muscular dystrophy. First generation technology is currently being tested in a clinical trial.

There is also international research ongoing to understand how it could be used to treat myotonic dystrophy and spinal muscular atrophy. The technology also has the potential to be developed into a therapeutic approach for several other conditions such as facioscapulohumeral muscular dystrophy (FSH) and Ullrich congenital muscular dystrophy.

The development of a gene therapy approach using a harmless virus to deliver a functional gene into cells has great potential as an effective treatment. Recently, the use of adeno-associated viruses has shown promising results in a clinical trial for limb girdle muscular dystrophy 2D and Duchenne muscular dystrophy.

It is now widely believed in the scientific community that it might not be just one treatment that will be needed to prevent muscle wasting in individuals affected by muscular dystrophy but a combination of different complementary approaches. We therefore will support the development of pharmacological interventions that address not only the primary cause of the disease but also secondary symptoms such as muscle inflammation and cell death, problems with the heart and those that will help to build muscle strength, such as the inhibition of myostatin.

In particular, high throughput drug screens can be an effective way to find new drugs that have a direct effect on the biological processes in a muscle cell that are causative of muscle disease. Enormous collections are now available to researchers that contain many thousands of drug-like molecules. In sophisticated experiments they are then tested on muscle cells that show the typical features of a condition to see if they can improve these features. The advantage of this method is that many drugs can be tested at the same time using automated, robotic technology.

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Paving the way to treatments

Muscular Dystrophy Campaign has made major contributions “to The the development of therapies in the past by funding several different approaches and assisting in the building of networks between laboratories to encourage collaborations. The new future strategy of the charity builds on this successful track record. It is both innovative and ambitious; essential ingredients to deliver effective treatments to patients.

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Professor Dame Kay Davies, Oxford University

The technology was successfully used for finding drugs that can increase the amount of a protein called utrophin in muscles cells. Utrophin has the potential to substitute for the dystrophin protein that is missing in boys with Duchenne muscular dystrophy.

A first candidate is currently being tested in clinical trial, but it is not yet known how well it will work.

Stem cells have the remarkable potential to develop into many different cell types in the body and replace and repair damaged tissue. A cell-based treatment approach could represent a powerful avenue to replace destroyed muscle or nerve cells and replenish the pool of stem cells in a person with a neuromuscular condition. The use of an individual’s own stem cells would avoid a possible immune reaction but most of the conditions we cover are inherited and this requires that either the defective gene be replaced or the genetic defect repaired. The development of a stem cell treatment for an inherited condition therefore represents a great challenge, but the long-lasting effect such a treatment could have makes it an approach worth pursuing.

In the next five years we see a need to fund research that aims: n

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to optimise exon skipping to make the technique more efficient for more boys and young men with Duchenne muscular dystrophy and to explore how the technology can be used for other conditions to explore promising new technology to repair the primary genetic defects underlying muscle and nerve disease to develop gene therapy approaches that use a virus or explore alternative methods to deliver a functional gene to muscle and/or nerve cells to identify drugs that target the primary underlying biological processes of muscle and nerve disease, aim to alleviate the secondary symptoms or help to improve muscle function to identify specifically second and third generation drugs that raise the level of utrophin production to treat boys and young men with Duchenne or Becker muscular dystrophy to further the understanding of stem cell biology and how stem cells are regulated with a clear focus on advancing the development of stem cell therapies.

The examples listed above are not intended to be an exhaustive list of therapeutic approaches that are currently being developed. We would therefore also consider funding alternative avenues that are not specifically mentioned but which would contribute to the development of potential treatments.

Spinal muscular atrophy The name spinal muscular atrophy (SMA) refers to several related neuromuscular condition that all have the same basic cause but differ considerably in age of onset and severity. SMA Type I, which is the most severe form of this condition, is the most common single genetic cause of death in infancy. There is currently no cure for SMA or treatment to stop its progression. Medical care and physical therapy may help prevent complications and ensure the best possible quality of life for those affected. SMA is caused by mutations in the Smn1 gene which can lead to a lack of Smn protein – which is vital for nerve cell survival. Among other strategies, researchers are investigating technology to restore expression of the protein. This could be achieved in several ways, and clinical trials to test exon skipping technology and potential small molecule drugs are underway around the world.

Our research strategy 2013 – 2018

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It is essential for clinicians to have clinical data, collected over a long time, available so that a decision can be made of how best to test a potential therapeutic intervention.

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STRATEGIC GOAL 2

To promote clinical trial readiness

Facioscapulohumeral muscular dystrophy Trying to understand the complex changes that occur in the muscles as a result of the mutation that causes facioscapulohumeral muscular dystrophy (FSH) has been a major challenge for scientists. Only now, more than 20 years after the mutation was originally identified, do they feel they are coming close to gaining an insight into the mechanisms behind the condition. The recent discovery of a gene that causes FSH type 2 has added to this wealth of knowledge. With this increase in our understanding, there has been a move towards the development of a therapy and a suggestion that exon skipping technology has the potential to be used to treat this condition. In preparation for this research into therapeutic approaches, the Muscular Dystrophy Campaign has supported the development of a registry for individuals with FSH. Over the coming years, the charity will continue to support the registry and will support further research into the development of therapies and further understanding of the molecular basis of this complex condition.

A key area for the charity in the coming years will be in investing in the national clinical infrastructure to bring promising technology into clinical trial more rapidly. Most of the conditions we cover are rare or ultra-rare and this poses a significant challenge for researchers carrying out clinical trials. Finding appropriate participants and ensuring that the right assessments are being used to measure the benefit of a potential drug or other therapeutic intervention is crucial for clinical trials to be successful. A growing tendency for a personalised treatment approach – where a drug may only treat a subset of people with a condition (inherent to technologies such as exon skipping), whereas an individual drug could only treat people with certain specific mutations – does add to the challenge.

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he charity aims to continue to provide support for patient registries that are crucial for the location and recruitment of individuals into clinical trials. They also present a fundamental tool for the pharmacological industry to plan national and international multi-centre studies. This is especially important for the coming years as we expect that the number of new clinical trials will rise and ongoing clinical trials will move into the advanced stages and a greater number of participants will be needed.

Most muscular dystrophies and related neuromuscular conditions are slowly-progressing conditions affecting muscle function and sometimes other organs. The level of muscle function, however, can be difficult to assess as it does not only affect the skeletal muscles, but it also has an impact on the heart and the respiratory muscles. It is therefore essential for clinicians to have clinical data, collected over a long time, available so that a decision can be made of how best to test a potential therapeutic intervention. Natural history databases such as the UK National Neuromuscular Database developed at the MRC Centre for Neuromuscular Diseases are tools that are urgently needed.

The charity has invested in the North Star and SMArtNet databases (for people with Duchenne muscular dystrophy and spinal muscular atrophy) and plans to continue investing in these areas. The establishment of professional national networks and the development of appropriate clinical evaluation tools such as the North Star Ambulatory Assessment for Duchenne muscular dystrophy will also be a focus in the future years as more clinical trials for other neuromuscular conditions will start and their success will have to be guaranteed.

The efficient running of clinical trials also requires specialist input from a clinical trial co-ordinator to help with the navigation of the stringent regulatory processes and the recruitment of suitable participants. The charity aims to continue providing support for these crucial roles at Muscle Centres of Excellence to maximise their participation in national and international studies and to ensure that people here in the UK will have early access to potential treatments.

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STRATEGIC GOAL 3

To support clinical trials and pilot studies Clinical trials are the gold standard against which to evaluate the benefit of a therapeutic intervention and are the final hurdles in the development of new treatments that are so desperately needed.

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he preparation of a clinical trial can take considerable time and resources and includes extensive safety tests in the laboratory to minimise potential health risks to the study participants. The collaboration of a number of researchers and clinicians with expertise from different areas is required to successfully prepare and carry out the first studies to evaluate safety and first proof of principle of a promising technology. But even these first phases of a clinical trial are expensive and come at a cost that is beyond the charity’s research budget.

In 2003, however, the charity was instrumental in establishing the MDEX consortium and successfully applying to the Department of Health and the Medical Research Council (MRC) to fund one of the first clinical trials to test the benefits of exon skipping technology. This is an area where we plan to play a role in the coming years: bringing experts together to conduct the first stages of clinical trials. We plan to do this alongside ongoing work by the Muscular Dystrophy Campaign to press government and statutory agencies to increase research funding into neuromuscular conditions.

There is also a need to conduct pilot studies, in a small number of people, aimed at testing already approved drugs based on the rationale of ‘repurposing’ these medicines for the benefit of people with neuromuscular conditions. Limited safety testing is necessary and studies carried out in the UK are often part of an international initiative involving several countries. Through our research programme we aim to continue to support these pilot studies because testing these drugs could represent an efficient and quick way to identify first potential treatments that target various symptoms of neuromuscular conditions.

Muscular Dystrophy Campaign is the only charity in the UK “thatTheprovides grants for clinical trials in muscle conditions. These trials are essential for developing new treatment options for patients with devastating muscle-wasting conditions. Clinical trials are expensive and time-consuming with lengthy bureaucratic hurdles, yet with support from the charity, advances such as the MDEX trial for Duchenne muscular dystrophy have been made. Without the valuable support, this would almost certainly have never happened.

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Dr Ros Quinlivan, Consultant Neurologist, Centre for Neuromuscular Disease, Queen Square, London

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Paving the way to treatments

Charcot-Marie-Tooth disease Charcot-Marie-Tooth disease (CMT) was first described in 1886. By the 1960s, as understanding of the condition increased, clinicians started to separate CMT into different types and it is now believed that CMT is a group of conditions with superficially similar symptoms which can be caused by mutations in at least 40 different genes. Recently, clinical trials have tested whether dietary supplements and exercise may be able to improve the quality of life of people with CMT. Although much of the research into CMT focuses on identifying the genes that cause the condition and carrying basic research into the biological mechanisms between mutations in these genes and the symptoms of the condition, clinical trials are also starting. These have focused on understanding whether lifestyle choices such as exercise or strentgth training, or taking dietary supplements could help people with the condition, but trials are now moving towards testing potential new treatments.

The collaboration of a number of researchers and clinicians with expertise from different areas is required to successfully prepare and carry out the studies to test safety and first proof of principle of a promising technology.

Our research strategy 2013 – 2018

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Our strategic

goals at a glance GOAL 1

To develop potential therapeutic approaches

GOAL 2

We will fund research to optimise exon skipping and explore its potential for other conditions, to develop technology that aims to repair the genetic defect, to identify drugs that target underlying biological processes and to further the understanding of stem cell biology.

To promote clinical trial readiness We will invest in the national clinical infrastructure by providing support for patient registries, national history databases and clinical trial co-ordinators.

GOAL 3

To support clinical trials and pilot studies We will fund small pilot studies based on the rationale of repurposing drugs for the benefit of people with neuromuscular conditions and plan to play a role in bringing experts together to conduct the first stages of clinical trials to test sophisticated new therapeutic approaches.

GOAL 4

To understand the cause of neuromuscular conditions A significant proportion of people with neuromuscular conditions have not received a diagnosis and the charity will continue to fund research as part of larger initiatives to find new disease genes and understand their role in causing the condition.

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GOAL 5

To build clinical and scientific capacity

GOAL 6

The charity will encourage young scientists and clinicians to take up a career in neuromuscular conditions to ensure that future generations have the same excellent quality they have today by providing PhD studentships and Clinical Training and Research Fellowships.

To improve quality of life

GOAL 7

We will fund research into improving clinical care, finding ways for better managing the different conditions and understanding those factors that have a positive impact on the quality of life for affected individuals as well as their families.

To foster sharing of knowledge and networking In the coming years we will encourage the establishment of a national and international infrastructure that allows researchers from different disciplines to efficiently communicate and collaborate to ensure the speedy translation of promising technology into a clinical benefit.

GOAL 8

To build partnerships We are keen to represent the patients’ views in European and international projects and to work together with other charities and funding institutions such as the Medical Research Council, Chief Scientific Office Scotland and the Wellcome Trust whenever a suitable opportunity arises.

Our research strategy 2013 – 2018

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It is part of our mission to ensure that one day everybody with muscular dystrophy or a related neuromuscular condition will receive an accurate diagnosis.

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Paving the way to treatments

STRATEGIC GOAL 4

To understand the cause of neuromuscular conditions Congenital muscular dystrophies The congenital muscular dystrophies are a diverse group of conditions and although the progression and biological mechanisms behind some of the conditions in this group are now reasonably well understood, a genetic diagnosis cannot yet be given for up to 30 percent of individuals thought to have a congenital muscular dystrophy. For a small number of the congenital muscular dystrophies however, the prospect of clinical trials is now a reality. The charity’s ongoing support for a clinical trial co-ordinator in London has allowed the Muscle Centre of Excellence at Great Ormond Street Hospital to take part in one of the first clinical trials for this group of conditions where a drug called omigapil will be tested for use in Ullrich congenital muscular dystrophy, Bethlem myopathy and merosin-deficient congenital muscular dystrophy. The charity will continue to provide support for the trial co-ordinators at Muscle Centres of Excellence, and will support the basic research that is needed to further understand, and subsequently develop treatments for, this diverse group of conditions.

Most of the 60 muscular dystrophies and related neuromuscular conditions the charity supports are caused by mutations in genes that are crucial for accurate functioning of the muscles or the nerves that transmit the electrical signal from the spine to the muscle fibre.

Finding and studying these genes opens the gateway for a better understanding of the underlying biological mechanisms leading to muscle weakness and wasting. It also provides crucial knowledge for clinicians to offer families accurate genetic counselling and give them choices in family planning. Most importantly, it is vital for the development of effective treatments.

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uchenne muscular dystrophy was the first condition for which the genetic defect was found. This was in 1987 and since then more than 100 other genes have been identified that can cause a muscular dystrophy or a related neuromuscular condition. However, there are still people with one of these conditions that do not receive a genetic diagnosis, with most of them carrying ultra-rare mutations.

In the last years, tremendous advances have been made in the development of technologies that can analyse every gene in a cell at the same time. These techniques are described as ‘whole genome’ or ‘whole exome’ sequencing. Today scientists can decipher a person’s DNA a thousand times faster than 20 years ago and genetic defects that affect only a very small number of people can be found quickly and efficiently.

The charity is currently funding such projects because it is part of our mission to ensure that one day everybody with a muscular dystrophy or related neuromuscular condition will receive an accurate diagnosis. For the coming years, the European Union and the Wellcome Trust have agreed to fund gene identification studies using whole genome sequencing on a large scale using significant resources. The charity will seek active involvement in these studies to address ethical issues concerning informed consent and the storage of biological samples, to ensure that the voice of our families is heard.

As enormous funding has been allocated by these funders, we feel it is justified to allocate a smaller proportion of our funding to such projects. We will still consider such projects in our annual grant round in the coming years but the priority will shift to projects that aim to study the function of these genes with a clear focus on developing therapeutic approaches.

Our research strategy 2013 – 2018

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STRATEGIC GOAL 5

To build clinical and scientific capacity The UK has an outstanding reputation for having some of the best scientists and clinicians in the field of neuromuscular disorders and the charity has played a crucial role in supporting the scientific community to establish its internationally leading position.

Encouraging young scientists and clinicians to take up a career in neuromuscular research has been central to our efforts to ensure that future generations of researchers have the same excellent quality as they have today.

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ne focus of our research programme is the provision of PhD studentships to encourage young science students to join one of the excellent research groups which we have in the UK. Through our usual rigorous peer review system we will only award applications that ensure the students will carry out cutting-edge science and will receive training within a high profile PhD programme.

Providing support for PhD students remains a strong focus of our research programme in the coming years.

We are also of the view that there is a need to provide Clinical Training and Research Fellowships to give young clinicians the opportunity to receive training at one of the Muscle Centres of Excellence in the UK to become neuromuscular clinicians. They will gain experience under the guidance of leading experts in all aspects of neuromuscular disorders at the same time as undertaking cutting-edge research. The aim is that after completing their training, the clinical fellows will take their expertise to clinics lacking expert knowledge where they will be able to speedily transfer new research advances into a clinical benefit.

from the Muscular Dystrophy Campaign made possible “myFunding clinical research fellowship at Newcastle and as a result I now have a framework on which to base my practice here at Oswestry.

The chance to spend three years in a centre dedicated to neuromuscular conditions and have close links with both the clinicians and the scientists was invaluable.

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Dr Tracey Willis, Consultant Paediatric Neurologist and former Muscular Dystrophy Campaign-funded Clinical Training and Research Fellow

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Limb girdle muscular dystrophy More than 20 genes have so far been identified that are known to cause limb girdle muscular dystrophy. Genetic tests are vital for clinicians to confirm an initial diagnosis and give families the information they need for further family planning.

The charity has supported Prof Kate Bushby’s laboratory in the Muscle Centre of Excellence at Newcastle University for more than 20 years and the funding has been essential for the Centre to establish an international reputation for research and care. Research here has led to the identification of numerous genes and this knowledge has been the basis for the development of potential treatments. But there are still about a fifth of people for whom the genetic defect has not been found. The recent award of a Clinical Training and Research Fellowship will allow the Centre to link its research activities with a European project aimed at using whole genome sequencing to identify new genes that cause limb girdle muscular dystrophy so rarely that conventional gene-identifying methods cannot be used.

STRATEGIC GOAL 6

To improve quality of life Although the development of therapeutic approaches has seen great advances in recent years, it might still take years for an efficient treatment to become available for most of the muscular dystrophies and related neuromuscular conditions. We also expect that the efficiency of the first treatments that come to the clinic might be limited and that some symptoms may persist.

Myotonic dystrophy The mutation that causes myotonic dystrophy was first discovered in 1992 by Muscular Dystrophy Campaign-funded scientists and, since then, work has been focused on understanding the underlying biological processes of the condition as well as trying to improve diagnostic techniques. More recently, the development of potential treatments has come to the fore, using exon skipping technology to eliminate the toxic molecule that is produced as a result of the mutation. With this move towards the development of treatments, and the concurrent interest from pharmaceutical companies, the charity made an award to fund the set-up of a UK registry for myotonic dystrophy type 1. This will make it easier to recruit participants when the time comes for clinical trials to begin, as well as help to improve standards of care for people with myotonic dystrophy. The charity will continue to invest in the infrastructure that will ensure the UK’s participation in these upcoming clinical trials and will support research into the development of other new therapies for this condition.

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his means that in the near future there is a need to fund research into improving clinical care, finding ways for better managing the different conditions and understanding those factors that have a positive impact on the quality of life for individuals with a neuromuscular condition as well as their families.

The charity has funded research into these areas in recent years and although this area is growing, the evidence for certain management strategies is weak. For example, there is anecdotal evidence that physiotherapy and hydrotherapy can have a positive impact on muscle pain and general wellbeing but the challenge is to identify criteria to assess and quantify their benefits. And although the belief that exercise damages the muscle in individuals with a muscular dystrophy has changed and is still changing, and small pilot studies suggest there could be a clinical benefit, there are no clear recommendations and exercise schemes that professionals can give to their patients.

There is a need for well-designed clinical trials that also consider patient-reported benefits to provide the clinical evidence for these interventions. The results of these studies might also provide information for healthcare providers to allocate resources into the right areas for people with neuromuscular conditions to receive the best standards of care.

A pilot study we recently funded explored the perceptions individuals with neuromuscular conditions have of their quality of life and found this is not always related to the severity of the disease. The aim was to understand the factors that have an impact on somebody’s beliefs about their condition and to devise ways of changing adverse perceptions to improve their quality of life. However, further studies are needed to confirm the initial findings and translate the results into clinical recommendations.

The charity is of the view that this area will continue to be a focus for funding through our competitive research programme. We would welcome well-designed feasibility and pilot studies into the benefit of physiotherapy and exercise programmes (as well as hydrotherapy) and projects that help individuals to better manage their condition and subsequently improve their quality of life.

Our research strategy 2013 – 2018

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STRATEGIC GOAL 7

To foster sharing of knowledge and networking The conditions the charity supports are rare or ultra-rare and some clinicians may never see a patient with a rare form of muscular dystrophy or one of the related neuromuscular conditions in their professional lives. Sharing knowledge and experience in the scientific community in the UK and internationally is crucial in shortening the time that individuals have to wait to receive an accurate diagnosis and receive the best standards of care.

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n the coming years, the focus of the scientific community will be on the translation of promising technology into clinical benefits. This requires the establishment of national and international infrastructure that allows researchers from different disciplines to efficiently communicate and collaborate.

Since 2008, the charity has organised, in partnership with the Medical Research Council (MRC) Centre for Neuromuscular Diseases, the UK Annual Translational Research Conference to bring together clinicians and scientists to showcase the latest research advances into neuromuscular conditions and highlight their translation into clinical benefits.

The meeting has become an integral part of the scientific calendar in the UK and the charity is planning to proceed with this successful partnership in the coming years.

The charity will also play an important part in providing platforms to facilitate the communication and collaboration among the scientific community as we have done in recent years. This will include considering support for Cochrane reviews of interventions for neuromuscular conditions. These form the basis of clinical guidelines and are both necessary precursors for clinical trials (topic 3) and also summarise the results from clinical trials (topic 4).

We will provide continuing support for the European Neuromuscular Centre (ENMC) located in Baarn in the Netherlands. This is a unique initiative established to facilitate communication and collaboration for researchers and professionals working in the field of neuromuscular conditions. The ENMC is solely funded by European patient organisations and brings the scientific community together through a series of workshops.

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Becker muscular dystrophy Becker muscular dystrophy is also caused by mutations in the dystrophin gene and although the symptoms are usually milder than those of Duchenne muscular dystrophy, affected individuals can still have difficulties with mobility, heart problems and sometimes breathing problems, all of which can have an impact on quality and length of life. In addition to funding research into developing new treatments for boys and young men with Duchenne muscular dystrophy that have a benefit for boys and young men with Becker muscular dystrophy, the charity is keen to fund research which could aid in the management of this condition, such as physiotherapy or exercise studies.

This may become particularly important in the coming years if exon skipping drugs for Duchenne muscular dystrophy reach the market as they are expected to change the symptoms of Duchenne muscular dystrophy into something akin to Becker muscular dystrophy.

Our research strategy 2013 – 2018

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We plan to give these families the opportunity, in partnership with us, to choose to fund projects that have passed our rigorous peer review process.

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STRATEGIC GOAL 8

To build partnerships The charity is committed to building partnerships with other funding agencies and patient organisations to combine resources to fund vital research that falls within one or more of the priority areas set out in this document.

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n the coming years we are keen to represent the patients’ views in European and international projects and to work together with other funding institutions such as the Medical Research Council (MRC), Chief Scientific Office (CSO) Scotland and the Wellcome Trust whenever a suitable opportunity arises.

In recent years we have seen the establishment of an increasing number of patient organisations and family funds that focus on a single condition. In the coming years we plan to broaden the involvement of these family funds; while we recognise that some families wish to invest considerable funds into research, the amounts they raise, however, might not justify the establishment of their own peer review process. There is concern that the lack of a rigorous peer review process could lead to families funding research projects of lesser quality. To maximise the resources available and to ensure only the best research is funded, we will focus in the next five to seven years on developing joint opportunities for the interested parties together. We plan to give these families the opportunity, in partnership with us, to choose to fund projects that have passed our peer review process. We have already established the Duchenne Forum and held a successful ‘Duchenne roundtable’ meeting where clinicians, researchers and representatives from other Duchenne muscular dystrophy organisations came together to discuss how we can combine our efforts to accelerate the development of potential treatments.

We are ready to work together with other patient organisations and family funds and will initiate and support activities that facilitate the establishment of partnerships that aim not only to avoid any duplication of efforts but also to jointly fund research.

Duchenne muscular dystrophy The gene that is mutated in Duchenne muscular dystrophy – dystrophin – was identified in 1987 and since then efforts have focused on the development of a treatment for this devastating condition. More than 25 years on, several different approaches, including two that were spearheaded by the Muscular Dystrophy Campaign, are now being tested in clinical trial. While we are keen to see these succeed, we also understand the importance of supporting the development of second generation drugs and technologies that may bring a greater clinical benefit and with it fewer side-effects for the boys, young men and manifesting carriers with this condition. Over the next five to seven years, our research focus for Duchenne muscular dystrophy will be on funding research that is directly relevant to the development of a new therapeutic approach or one that will enhance and optimise a strategy already in clinical trial.

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Our

commitments Our families and supporters are at the heart of everything we do and we are committed to involving them in every aspect of our work. This way we can make sure that the research we fund reflects the needs and requirements of people directly or indirectly affected by muscular dystrophy or a related neuromuscular condition.

Research communications Our families and supporters have a keen interest in receiving informationand updates about research the charity is funding and about the latest research developments happening elsewhere in the world. The charity has a role to play in interpreting and translating these complex scientific scenarios into a language that is easy to understand. This will increase transparency and make scientific advances accessible and more easily understandable to a wider audience.

In recent years we have developed various channels for the dissemination of research advances and, with the help of written contributions from our scientists, we publish regular updates on our website and in our quarterly research magazine Target Research.

We will continue to build upon our excellent research communications service by incorporating digital tools such as videos and podcasts to introduce new research projects and present their results in a way that is easy for a lay audience to engage with and understand.

And we will also strengthen our position as the authoritative voice in the UK on current relevant scientific affairs by giving expert commentaries to the press throughout the year.

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Funding high quality science

How we will fund research

The charity remains committed to funding only high-quality science that is relevant to the development of treatments and the improvement of quality of life for individuals with muscular dystrophy and related neuromuscular conditions.

In the next five to seven years, the Muscular Dystrophy Campaign will continue to identify and invest in the most promising science, funding world-class pioneering research that helps us to achieve the strategic aims set out within this document.

Our funds are raised through donations made by our families and supporters and we have a duty to ensure that this money is used wisely and invested in research that has the greatest chance of having an impact on the lives of individuals affected by neuromuscular conditions.

We are committed to using a rigorous peer review process according to the guiding principles set by the Association of Medical Research Charities to assess grant applications. Peer review subjects the quality of scientific ideas to independent scrutiny by qualified experts (peers).

Using peer review ensures that the research is: n

scientifically valid, significant and original

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timely and achievable

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not duplicating other work

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using appropriate methodologies

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carried out by researchers with the right skills and facilities

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value for money.

Using peer review ensures that we are fully accountable to our supporters and that each research project is assessed in a balanced, independent and impartial way.

A voice and choice for our families We have already put in place various mechanisms for our supporters and families to ensure their voices are heard with regard to communicating and funding research. Our Talk Research group has been instrumental in shaping the way we communicate research and has helped us to find the appropriate language and topics we talk about. Our Lay Research Panel has become an inherent part of our peer review process assessing the importance and relevance of each project from the perspective of someone affected by muscular dystrophy or a related neuromuscular condition. The members have been crucial in initiating dialogue with the scientific experts on our Medical Research Committee and together they decide which research projects warrant funding.

The charity will continue to fund research mainly on a reactive basis. This means we will not commission specific pieces of research but we will hold a competitive annual call for grant applications. In exceptional circumstances we will consider an application outside the grant round that will be subjected to a peer review similar to those of the annual grant round.

We will fund combinations of the following types of grants as appropriate and dependent on the budget and nature of the grant call: n project grants of one to three years n

pump-priming grants of up to one year

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PhD Studentships of three to four years

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Clinical Training and Research Fellowships

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infrastructure grants including registries, natural history databases and clinical trials co-ordinators

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international projects will be considered where there is UK participation.

With the help of our Lay Research Panel and our Medical Research Committee, the charity will also identify specific problems or neglected areas of research and may put out highlighted calls for applications to address these areas. In addition, where there are sufficient restricted funds available for research into a specific condition, the charity may put out a restricted call for applications into that area.

These highlighted and restricted calls may be put out instead of, or in addition to, our annual open call for applications. Where it is felt there are insufficient numbers of researchers within the UK to ensure that a highlighted/restricted call remains competitive, the charity will invite selected researchers from overseas to apply.

Our research strategy 2013 – 2018

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Muscular Dystrophy Campaign 61A Great Suffolk Street London SE1 0BU t: 020 7803 4800 e: research@muscular-dystrophy.org w: www.muscular-dystrophy.org Registered Charity No. 205395 and Registered Scottish Charity No. SC039445 Cover illustration: smartboy10/istock. Photographs: Chris O’Donovan/Muscular Dystrophy Campaign