More effective treatments for this generation of patients living with DMD are urgently needed.
As the UK's largest funder of DMD research, we're funding groundbreaking science to treat not only the symptoms of the disease, but also the underlying causes.
Research we're funding
Duchenne UK is funding revolutionary scientific research to transform the lives of those affected by DMD.
Most of the current treatments for DMD do not address the underlying cause: the body’s inability to produce dystrophin. We want to better understand and target the causes of DMD so that we can stop the disease in its tracks. That’s why we’re funding revolutionary treatments like gene therapy, to replace the missing dystrophin gene lacking in people with DMD.
We also recognise the urgent need to improve the quality of life of those living with DMD today. We fund research into treatments and therapies to treat DMD’s severe symptoms and help patients live longer, healthier lives. This includes improving muscle function, reducing DMD’s impact on the heart and lungs, and changing lives through technology.
For an explanation of medical terminology, visit our research glossary.
DMD is caused by a genetic mutation that means the body is unable to produce the dystrophin protein. Dystrophin is essential for strengthening and protecting muscle fibres. We are funding groundbreaking research into ways of replacing the missing dystrophin in people with DMD.
One of the most promising treatments for DMD is gene therapy. This involves delivering new genetic material to cells to overcome errors (or mutations) on the dystrophin gene.
DMD is an inherited, genetic disease. A gene is a very large molecule, and the gene for dystrophin is the longest known human gene.
To treat DMD, we need to repair or deliver a new copy of this gene to every cell in the body where it is needed.
In the last few years, huge progress has been made in gene therapy to treat DMD.
How does gene therapy work?
Gene therapy is the delivery of working copies of a gene to the cells that need it.
Our cells have evolved ways of preventing intrusion from foreign molecules. To overcome this, researchers use vectors to carry the new gene into the cell. Currently, the most promising approach is based on the use of a relatively harmless virus called Adeno-associated virus (AAV) as the vector, as viruses have evolved to be able to get inside our cells.
Once inside the cell, viruses deliver their genetic material, and force the cell to make many copies of the virus. With most viruses, like colds or flu, this makes us feel unwell. However, if scientists remove the unwanted, disease-causing viral genes and replace them with genes that the body needs, like the dystrophin gene, it could help the body to produce the proteins it needs.
Researchers have created a shortened version of the dystrophin gene called microdystrophin so that it can fit into the AAV vector. In animal studies, microdystrophin has resulted in improved muscle function.
What are the challenges of gene therapy?
Gene therapy for DMD poses some big technical challenges. This includes the body developing an immune response to the AAV, which prevents it from reaching cells. As the dystrophin gene is the longest in the body, it is also a challenge to find a delivery system which is large enough to carry it.
Watch our video below to understand more about the challenges in gene therapy:
What gene therapy research is Duchenne UK funding?
Duchenne UK is funding research to overcome the challenges of gene therapy in DMD, with projects looking at:
Progressing gene therapy into clinical trials in the UK through the DMD Hub
Preventing the immune responses that can prevent AAVs from entering the body and delivering microdystrophin
Exploring alternative delivery vectors for gene therapy that could carry a larger dystrophin gene
Gene editing, or genome editing, is a technology that enables the editing of parts of the genome (your body’s set of genetic instructions) by removing, adding or altering the DNA sequence.
This is an exciting new area of research that has the potential to make precise, targeted changes to correct the mutations that cause diseases like DMD.
How does gene editing work?
Researchers have developed techniques that use enzymes (called endonucleases) that work like a pair of molecular scissors to cut the DNA at a specific location. A guide RNA (gRNA) ensures that the enzyme cuts the DNA in the right place.
Once the DNA has been cut, the body tries to repair it. This removes the deletion that means dystrophin cannot be produced, and allows for the genetic sequence to be read.
This has not yet been tested in humans and has been mainly tested in animal models. As with gene therapy, there are several challenges to delivering it as a treatment. It also uses adeno-associated viruses (AAVs) to deliver the genetic material to the cell, and there is still work to be done to ensure that the gRNA only targets the area it is supposed to.
Although there are still many hurdles to overcome, this is a very promising area for DMD.
What gene editing projects are Duchenne UK funding?
We are funding research into making gene editing a possibility for DMD, including:
Early stage research looking at the use of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats), a genome-editingtechnology, to repair deletions in the dystrophin gene. (the majority of DMD cases are caused by deletion)
Early stage research looking at the use of CRISPR to repair duplications on the dystrophin gene (approximately 10 – 15% of DMD cases are caused by duplication)
Testing CRISPR techniques in-vivo (in a mouse model)
The active part of the dystrophin gene is made up of 79 pieces called exons. These exons link together to form a code that is read in the cells so that the protein dystrophin can be made.
In DMD, some of the exons are not readable. The result is that very little or no dystrophin is made.
How does exon skipping work?
Exon skipping drugs hide or ‘patch’ the missing piece so that the exons fit together again and can be read. This means that a functional, although shorter, dystrophin protein can be produced by the body.
Exon skipping has been shown to work in animal models of DMD.
As the exon skipping drug is designed to skip over a particular exon, different versions need to be made depending on which exons needs to be skipped. This is because people with DMD have different genetic mutations that cause the disease. The most common mutation is around exon 51 and accounts for approximately 13% of cases of Duchenne.
EXONDYS 51 (previously known as eteplirsen) is an approved treatment in the USA that targets the 51 mutation. Existing treatments are administered by injection.
Ataluren (sold under the brand name Translarna) is an approved treatment in the UK which treats DMD resulting from a nonsense mutation.
What exon skipping research is Duchenne UK funding?
We are funding research into more effective exon skipping treatments that target different mutations. This includes:
Developing more effective and safer exon skipping treatments
Investigating whether exon skipping can help to restore dystrophin in the brain
Treating the symptoms of DMD
Our ultimate aim is to find a cure for DMD, but we also want to improve the quality of life of those living with DMD today. We fund research into treatments and therapies that could treat the symptoms of DMD and help patients live longer, healthier lives.
Developing a brand-new drug takes a huge amount of time, money and effort. Meticulous testing, delays and barriers mean that turning a promising molecule into an approved drug often takes more than 14 years. We want to develop treatments for this generation of boys living with DMD, and repurposing existing drugs is one way of reducing this time frame, reducing costs, and improving success rates.
Repurposing (or repositioning) means taking a drug which is already approved for one disease and using it to treat another. These have already been tested in humans, so we know how they work and how safe they are. Because repurposing builds on previous research, new therapies could be ready for clinical trials quickly, speeding up their review by regulatory agencies, and their availability to treat DMD.
What repurposing drugs research is Duchenne UK funding?
Investigating the potential of a drug called Tamoxifen, currently used to treat breast cancer, to treat DMD by reducing fibrosis and delaying disease progression
Investigating the potential of the combination treatment of Metformin and L-Citruline, used to treat type 2 diabetes, in delaying the progression of DMD
A lack of dystrophin means that as muscles become damaged by everyday use, and are unable to be repaired. This begins a process of inflammation and fibrosis, which eventually leads to the loss of muscle cells.
A type of steroid called corticosteroids are currently the only treatment which is effective at keeping children with DMD walking for longer, but they have many negative side effects. We therefore want to find safer and more effective treatments.
What research into improving muscle function is Duchenne UK funding?
We are funding research into alternative treatments that prevent inflammation and fibrosis, as well as promote muscle growth. This includes investigating:
The effect of testosterone on growth and muscle function
The use of beta-blockers and ace inhibitors (drugs used to treat heart disease) in protecting the heart muscles of DMD patients
The generation of new, healthy muscles to replace damaged tissue through stem cell research
The development of an alternative to corticosteroids, Vamorolone, that could have a similar impact with less severe side effects
The combination of a variety of approved medicines to reduce fibrosis, improve muscle function, and regenerate muscle in DMD (see repurposing drugs)
The use of hydrotherapy to benefit patients’ mobility
Many dietary supplements, or nutraceuticals, are thought to have anti-inflammatory or anti-oxidant effects. We know that DMD progression is worsened by inflammation and oxidative stress, so it’s thought that nutraceuticals could have some therapeutic benefit to patients.
Many parents report using supplements for their children but little evidence currently exists on whether they are safe and effective.
What research into dietary supplements is Duchenne UK funding?
We’re funding research into the benefits of certain supplements for DMD patients, including:
The use of taurine, an amino acid, to improve muscle strength and reduce inflammation in DMD.
The effects of Vitamin B3 on improving regeneration of muscle and help to retain muscle tissue
We also previously funded research into soy products, a popular supplement that families reported giving to children with DMD, which were found to be ineffective in slowing disease progression.
Technology is constantly developing, yet the tools available to help disabled people live independent lives are outdated. We want to harness innovation to give people living with muscle-wasting conditions like DMD a better quality of life.
What research into technology is Duchenne UK funding?
We are excited by the potential of technology to help transform the lives of people with DMD, and other disabilities, and are funding cutting-edge research and product design in this area. This includes:
Developing a new wheelchair (the DreamChair) for young people with the latest design and technology features, in partnership with Whizz-Kidz and the University of Edinburgh
Developing wearable, assistive clothing (the Solid Suit) that could help people with DMD with movement
Understanding DMD and the impact of treatments
In order to develop a treatment, it is vital to understand how the disease progresses. By better understanding DMD and how it affects the body, scientists can then target elements for correction.
By improving the ways in which we collect and analyse data from DMD patients, we have a much better chance of proving whether treatments are effective or not. This not only speeds up the drug development process, but is essential to getting treatments approved so that patients can access them.
What is Duchenne UK funding in this area?
We are funding studies that will help us to better understand the progression of DMD and better measure the difference that treatments make. This includes:
Developing a set of Patient Reported Outcomes so that patients can record the day-to-day differences a treatment makes during clinical trials. This will provide a more patient and caregiver-focused evaluation, so that treatments are better assessed in trials and when being considered for approval by regulatory agencies.
Increasing our understanding of how DMD progresses by analysing data from a six-year clinical trial of corticosteroid treatments. This data analysis will help us reduce the use of placebos in future trials, improve the way we measure outcomes, as well as better understand which corticosteroid treatments are safest.
Monitoring the hearts of DMD patients to understand the prevalence of arrhythmias (heart rhythm problems) and cardiac scarring (when muscle is replaced with scar tissue). This is so that heart problems can be better detected and sudden deaths from heart failure can be prevented.
Developing minimally-invasive biomarkers (measurable indicators of the severity of a disease) to measure muscle health. Current methods, which require the use of MRI scans and muscle biopsies, are invasive, expensive and time consuming. Researchers are looking at ways of measuring muscle health using blood and urine samples instead, so that diagnosing and monitoring DMD is easier and it is quicker and easier to evaluate treatments.
Before a potential treatment can be tested on humans in a clinical trial, researchers use animal models of the disease to understand the effectiveness of a treatment and its potential side effects.
The most commonly used animal model in DMD is called the mdx mouse. These are mice that have a mutation in the dystrophin gene, like humans with DMD. However, they show milder symptoms than humans, so we cannot guarantee that treatments that are effective in mdx mice will be equally effective in clinical trials. This means that research is held back by the lack of small animal models that are comparative to humans with DMD.
What research is Duchenne UK funding in this area?
We are funding research to increase the chance of potential treatments being effective in humans following animal studies. This includes:
Improving understanding of how the disease progresses in a new mouse model, the D2-mdx mouse, vs. the classic mdx model
Disappointing findings in anti-inflammatory drug repurposing project
Duchenne UK is disappointed to announce that a project investigating the potential of montelukast, an existing anti-inflammatory drug for asthma, to treat DMD failed to show benefit in a pre-clinical study.
New study to understand DMD patients’ and caregivers’ attitudes towards gene therapy launched
In a new transatlantic collaboration, Duchenne UK and the DMD Hub, PPMD and RTI International are conducting a study to explore attitudes towards gene therapy and gene editing from adults with Duchenne muscular dystrophy (DMD), parents and caregivers of children with DMD, and clinicians.
Clinical Trials Lectureship (Newcastle). End of project report summary
The Clinical Trials Lectureship grant enabled Dr Michela Guglieri to act as the Clinical Research Team Leader within the John Walton Muscular Dystrophy Research Centre in Newcastle
Serious adverse event on Pfizer’s Phase 1B gene therapy trial
Last night we heard news from our friends at PPMD in the US that a young man has died while participating in Pfizer’s Phase 1B Open-Label study. Read Pfizer's statement to the community.
Data from wearable devices approved for use in Duchenne muscular dystrophy clinical trials
The European Medicines Agency (EMA) has approved the first measure collected using a digital wearable device for use in clinical trials for Duchenne muscular dystrophy.
If you would like to discuss an idea for a research project or make a proposal for us to consider funding, please contact us in the first instance at [email protected]
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