A promising new horizon for DMD research
By Dr Alessandra Gaeta, Director of Research & Development, Duchenne UK
Organised by the World Muscle Society, the World Muscle Congress took place from 3-7 October in South Carolina, United States.
It was an important opportunity for people from around the world who are working to help those with neuromuscular diseases such as Duchenne muscular dystrophy (DMD) to meet, update each other about and discuss the latest developments in neuromuscular diseases.
This wide range of over 900 attendees included researchers, clinicians, and representatives from the pharmaceutical industry, and several patient organisations.
Focus of congress
I attended as the Duchenne UK representative, and welcomed its focus on translational research, which is research that generates insights and knowledge that can be directly translated in the clinic.
The following themes were explored:
- Understanding phenotypic and genetic diversity in neuromuscular disorders
- Pathobiology of neuromuscular expansion disorders
- The effect of lifestyle, exercise and nutrition on neuromuscular pathology and outcomes
The programme included new developments in the preclinical and clinical treatment pipeline, outcome measures and patient registries, as well as clinical care.
Of the 500 posters that attendees displayed at the congress to present their work, 80 focused on DMD research.
DMD research highlights
There was a wide range of DMD research covered at the congress. Here are a few highlights from presentations and posters I found particularly promising.
Exercise in DMD
Research is taking place to assess the value and potential benefit of monitored exercise in both ambulant (walking) and non-ambulant (non-walking) people with DMD.
Researchers in the US and Europe are running studies to evaluate exercise as a potential therapeutic approach for DMD. Of particular interest was the work presented by Dr Tanja Taivassalo from the University of Florida, which monitored the exercise of ambulant boys using special cycling and wearable devices. Her research showed regular exercise can have a positive impact on muscle strength in DMD, leading to increased activity without putting the heart at risk.
Dystrophin in the brain
One project that was looking at dystrophin levels in the brain had some exciting data. Dr Catapano from University College London has been studying the different types of dystrophin in the brain of healthy humans to understand where they are located and what their role might be. He will soon start translating this understanding to DMD. He hopes to use this research to help understand what the lack of dystrophin in the brain means for people with DMD, and its link to specific neurodevelopmental and other cognitive delays.
With gene therapy for DMD likely to be approved in the UK in the next year, it was very good to see how much research is taking place to improve its current limitations as a treatment modality in DMD.
Researchers at the Nationwide Children’s Hospital in Ohio and Ohio State University have undertaken research on a new gene therapy treatment that showed it was possible to restore full length dystrophin in rare types of DMD mutation. This demonstrates the value of bespoke gene therapy to restore full length dystrophin, giving hope for treatments to patients with rare, untreatable mutations.
Another project looked at combining gene therapy with exon skipping. Pharmaceutical company Sarepta undertook research on a mouse by giving it an exon skipping drug and treating it with gene therapy. They found that this combination was safe, led to higher levels of dystrophin expression, and that the two treatments didn’t interfere with each other. This is encouraging and suggests that patients on an exon skipping therapy may continue to take it if they subsequently receive gene therapy.
A study by Sarepta looked at ways to manage unwanted antibody response to adeno-associated viruses (AAV) gene therapy in DMD. Research on monkeys with DMD found that imlifidase (a drug used in kidney transplants) can reduce the antibody response to the AAV vector when given before gene therapy treatment. The results of this study are encouraging and could lead to an approach being tested on humans. This could potentially enable boys who are currently excluded from gene therapy, due to pre-existing antibodies against AAV, being able to be treated with it.
Exploring new treatment options
Finally, although gene therapy is showing so much promise, it is crucial that there is continued focus on other possible DMD treatments too. One that was especially interesting was an approach that combines genomic exon skipping, using CRISPR-Cas9, with lipid nanoparticles as a delivery mechanism. Undertaken by the pharmaceutical company Takeda and the Center for iPS Cell Research and Application (CiRA) at Kyoto University, the research has found that, in the mouse, this approach led to high efficiency of delivery and high levels of dystrophin expression in the muscle tissue.
A promising new horizon for DMD research
It was exciting to see so many new areas of emerging research and I look forward to discussing them with our Scientific Advisory Board, as we develop our new research strategy. It was also lovely to meet in person some of our collaborators and discuss new research ideas.
Watch this space for more updates as we continue to develop these into projects that you could support.