Webinar Recording: Understanding the role of dystrophin in the brain in DMD/BMD
The recent BIND Webinar brought together patients, caregivers, and researchers with a shared interest in advancing our understanding of brain comorbidities in Duchenne and Becker muscular dystrophies (DMD/BMD). Hosted by the World Duchenne Organization, this webinar provided key insights into the BIND (Brain Involvement in Dystrophinopathies) Project, an international research initiative dedicated to studying learning and behavioural challenges in DMD/BMD.
Professor Francesco Muntoni explained the goals, findings, and future directions of the BIND Project. In addition to this, Dr Amel Saoudi, Dr Hermien Kan and Dr Jos Hendriksen presented the latest findings from mouse models, MRI brain studies, and cognitive and behavioural assessments, offering a comprehensive look at brain comorbidities in DMD/BMD.
Monday September 23, 2024
Hosted by: World Duchenne Organization
Speakers: Prof Francesco Muntoni, Dr Amel Saoudi, Dr Hermien Kan, Dr Jos Hendriksen, Elizabeth Vroom
Webinar: Understanding the role of dystrophin in the brain in DMD/BMD
Professor Francesco Muntoni opened the webinar with an introduction to the BIND Project. Funded by the European Commission, the BIND Project focused on understanding how DMD/BMD impact the brain. Unlike other muscular disorders, DMD/BMD are known to affect both physical and neurological health, leading to cognitive and behavioural challenges in many patients.
Prof. Muntoni explained that BIND aims to provide new insights that could lead to improved diagnostic tools and treatment options for people living with DMD/BMD Through a series of studies involving mouse models and advanced imaging techniques, researchers have been able to better understand the correlation between the site of the individual DMD mutations and the brain involvement that can affect some of the affected DMD/BMD individuals. They have also been able to observe changes in brain structure and function, contributing valuable data to the scientific community.
Key findings
The BIND Project’s research is divided into several major components, each exploring a unique aspect of how these dystrophies impact the brain and behaviour.
1. Mouse model studies
Dr Amel Saoudi from CNRS – NeuroPSI, Paris-Saclay France talked about the mouse model studies that were performed. This work aims to understand the biochemical and neurological pathways affected by DMD. Mouse models are genetically modified to mimic as close as possible the muscular and neurological symptoms seen in human DMD. This enables researchers to study disease progression closely and better understand the underlying mechanisms in order to develop efficient therapies.
Studies using these models reveal insight into how the lack of dystrophin—a protein crucial for muscle health—also affects brain functions, particularly in regions associated with emotions, learning and memory. This has implications for understanding why people with DMD/BMD may experience cognitive challenges, such as attention deficits, learning and memory issues or emotional disturbances.
2. MRI brain studies
Next, Dr Hermien Kan from Leiden University Medical Center delved into the MRI brain studies that were conducted by the BIND Project. In the project, different types of scans have been performed. With structural scans the project we looked into the volume of different tissues types of the brain, grey matter that reflect cellular bodies and white matter that reflects the dendrites of neuronal cells. In addition, scans were performed that looked at the structural and functional connections and to the perfusion of the brain.
Previous data are mainly available from people with DMD, while MRI brain data from people with BMD are scarce. These previous data mainly showed reductions in grey matter volume and brain perfusion, and changes in structural and functional connectivity in DMD. Upon analysis of the scans obtained in BIND, which we will do in the following 12 months, we will obtain insight into the changes in the brains of people with DMD/BMD and link them to cognitive and behavioural function.
3. Cognitive and behavioural assessments
Thirdly, Dr Jos Hendriksen from Kempenhaeghe presented how the BIND Project focused on developing reliable assessment procedures for developing neurocognitive and behavioural functioning. The process of harmonization of assessment procedures over the seven EU centres was described. A large set of clinical data (for example on intelligence, memory, academics, behavioural functioning) is now available of more than 300 DMD/BMD patients and will be analysed in the next months/year. Some preliminary data were presented and show promising results. Further work is needed to analyse all data and to develop for example a DMD/BMD specific test kit for both neurocognitive and behavioural functioning. One other aim of the project is also to develop a screening tool to detect DMD/BMD patients who are at risk for brain related comorbidities. This tool has been developed and was distributed by the WDO.
Next steps
Professor Muntoni concluded the webinar with a discussion on the future directions of the BIND Project. The project’s ongoing studies will continue to deepen our understanding of how DMD/BMD affect learning and behaviour, and on the role that dystrophin has in the brain, and on therapeutic strategies to also increase dystrophin production in the brain. Additionally, the consortium is exploring potential therapeutic strategies that could target neurological symptoms directly, opening new possibilities for comprehensive care. The consortium has now established links with specialists working in the field of brain involvement in DMD across Europe and US, to deal more effectively with these complications, when present.
In addition to improving patient care, the findings from the BIND Project hold promise for shaping new guidelines for diagnosing and managing the neurological aspects of these dystrophies. By bridging the gap between muscular and neurological research, the BIND Project aims to pave the way for holistic treatment approaches that address both physical and cognitive health.
Conclusion
The BIND Webinar highlighted significant advancements in the study of brain comorbidities in DMD/BMD, demonstrating the importance of understanding neurological involvement. With studies on mouse models, MRI brain imaging, and cognitive assessments, BIND is helping to create a future where patients can receive more targeted and effective care for learning and behavioural challenges.
Finally, the World Duchenne Organization and the BIND Project are committed to educating the community and advancing research to improve patient outcomes.
For more information, watch the full recording of the BIND Webinar.
